Blood-Brain Barrier: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Brain Edema: Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6)Transendothelial and Transepithelial Migration: The passage of cells across the layer of ENDOTHELIAL CELLS, i.e., the ENDOTHELIUM; or across the layer of EPITHELIAL CELLS, i.e. the EPITHELIUM.Occludin: A MARVEL domain protein that plays an important role in the formation and regulation of the TIGHT JUNCTION paracellular permeability barrier.Brain Injuries: Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.Endothelial Cells: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Evans Blue: An azo dye used in blood volume and cardiac output measurement by the dye dilution method. It is very soluble, strongly bound to plasma albumin, and disappears very slowly.Tight Junctions: Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. (Alberts et al., Molecular Biology of the Cell, 2nd ed, p22)Microvessels: The finer blood vessels of the vasculature that are generally less than 100 microns in internal diameter.Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Encephalitis: Inflammation of the BRAIN due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see ENCEPHALITIS, VIRAL) are a relatively frequent cause of this condition.Astrocytes: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Nanoparticles: Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.Mice, Inbred C57BLDrug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.Choroid Plexus: A villous structure of tangled masses of BLOOD VESSELS contained within the third, lateral, and fourth ventricles of the BRAIN. It regulates part of the production and composition of CEREBROSPINAL FLUID.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Neuroglia: The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Stroke: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Octanols: Isomeric forms and derivatives of octanol (C8H17OH).Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Brain Mapping: Imaging techniques used to colocalize sites of brain functions or physiological activity with brain structures.Cerebrospinal Fluid: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.Infarction, Middle Cerebral Artery: NECROSIS occurring in the MIDDLE CEREBRAL ARTERY distribution system which brings blood to the entire lateral aspects of each CEREBRAL HEMISPHERE. Clinical signs include impaired cognition; APHASIA; AGRAPHIA; weak and numbness in the face and arms, contralaterally or bilaterally depending on the infarction.Brain Stem: The part of the brain that connects the CEREBRAL HEMISPHERES with the SPINAL CORD. It consists of the MESENCEPHALON; PONS; and MEDULLA OBLONGATA.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Cerebrovascular Circulation: The circulation of blood through the BLOOD VESSELS of the BRAIN.Matrix Metalloproteinase 9: An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.Blood-Retinal Barrier: A specialized transport barrier, in the EYE, formed by the retinal pigment EPITHELIUM, and the ENDOTHELIUM of the BLOOD VESSELS of the RETINA. TIGHT JUNCTIONS joining adjacent cells keep the barrier between cells continuous.Brain Abscess: A circumscribed collection of purulent exudate in the brain, due to bacterial and other infections. The majority are caused by spread of infected material from a focus of suppuration elsewhere in the body, notably the PARANASAL SINUSES, middle ear (see EAR, MIDDLE); HEART (see also ENDOCARDITIS, BACTERIAL), and LUNG. Penetrating CRANIOCEREBRAL TRAUMA and NEUROSURGICAL PROCEDURES may also be associated with this condition. Clinical manifestations include HEADACHE; SEIZURES; focal neurologic deficits; and alterations of consciousness. (Adams et al., Principles of Neurology, 6th ed, pp712-6)Blood-Air Barrier: The barrier between capillary blood and alveolar air comprising the alveolar EPITHELIUM and capillary ENDOTHELIUM with their adherent BASEMENT MEMBRANE and EPITHELIAL CELL cytoplasm. PULMONARY GAS EXCHANGE occurs across this membrane.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Contrast Media: Substances used to allow enhanced visualization of tissues.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Blood-Testis Barrier: A specialized barrier, in the TESTIS, between the interstitial BLOOD compartment and the adluminal compartment of the SEMINIFEROUS TUBULES. The barrier is formed by layers of cells from the VASCULAR ENDOTHELIUM of the capillary BLOOD VESSELS, to the SEMINIFEROUS EPITHELIUM of the seminiferous tubules. TIGHT JUNCTIONS form between adjacent SERTOLI CELLS, as well as between the ENDOTHELIAL CELLS.Communication Barriers: Those factors, such as language or sociocultural relationships, which interfere in the meaningful interpretation and transmission of ideas between individuals or groups.

Involvement of tumor necrosis factor alpha and interleukin-1beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae. (1/3796)

Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h. This was indicated by a significantly higher mean convulsion score and an increased number of mice responding with clonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti-murine TNF-alpha (anti-mTNF-alpha) or anti-murine IL-1beta (anti-mIL-1beta) 30 min prior to administration of Shigella sonicate abolished their enhanced response to PTZ at 7 h. Mean convulsion scores were reduced by anti-mTNF-alpha from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1beta from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-alpha also reduced the percentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1beta reduced it from 53 to 21% (P = 0. 012). Neutralization of TNF-alpha or IL-1beta did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-alpha and IL-1beta play a role in the very early sensitization of the central nervous system to convulsive activity after S. dysenteriae administration. Similar mechanisms may trigger neurologic disturbances in other infectious diseases.  (+info)

Drug-protein binding and blood-brain barrier permeability. (2/3796)

The permeability surface area (PS) product, an index of permeability of the blood-brain barrier (BBB), was measured by using the in situ perfusion method. In the cerebral circulation, the fraction of drug that permeates into the brain through the BBB is not only the unbound fraction but also the fraction dissociated from the protein in the perfusate. The sum of these two fractions, the apparent exchangeable fraction, was estimated by fitting the parameters of the BBB permeability under the condition of varying BSA concentrations in the perfusate. The unbound fraction of drugs in a buffer containing 0.5 mM BSA was measured by using the ultrafiltration method in vitro, and the apparent exchangeable fraction was measured in vivo by using the intracarotid artery injection method. The apparent exchange fraction was 100% for S-8510, 96.5% for diazepam, 90.9% for caffeine, 38.3% for S-312-d, 33.1% for propranolol, and 6.68% for (+)-S-145 Na, and each of these was higher than the corresponding unbound fraction in vitro in all drugs. The apparent exchangeable fractions, for example, were 8 times higher for diazepam and 38 times for S-312-d than the unbound fractions in vitro. The apparent exchangeable fraction of drugs was also estimated from the parameters obtained with the perfusion method. Because drugs can be infused for an arbitrary length of time in the perfusion method, substances with low permeability can be measured. The apparent exchangeable fractions obtained with this method were almost the same as those obtained with the intracarotid artery injection method.  (+info)

Novel, highly lipophilic antioxidants readily diffuse across the blood-brain barrier and access intracellular sites. (3/3796)

In an accompanying article, an in vitro assay for permeability predicts that membrane-protective, antioxidant 2,4-diamino-pyrrolo[2, 3-d]pyrimidines should have improved blood-brain barrier (BBB) permeation over previously described lipophilic antioxidants. Using a first-pass extraction method and brain/plasma quantification, we show here that two of the pyrrolopyrimidines, one of which is markedly less permeable, readily partition into rat brain. The efficiency of extraction was dependent on serum protein binding, and in situ efflux confirms the in vitro data showing that PNU-87663 is retained in brain longer than PNU-89843. By exploiting inherent fluorescence properties of PNU-87663, its distribution within brain and within cells in culture was demonstrated using confocal scanning laser microscopy. PNU-87663 rapidly partitioned into the cell membrane and equilibrates with cytoplasmic compartments via passive diffusion. Although partitioning of PNU-87663 favors intracytoplasmic lipid storage droplets, the compound was readily exchangeable as shown by efflux of compound from cells to buffer when protein was present. The results demonstrated that pyrrolopyrimidines were well suited for quickly accessing target cells within the central nervous system as well as in other target tissues.  (+info)

Inhibition by lead of production and secretion of transthyretin in the choroid plexus: its relation to thyroxine transport at blood-CSF barrier. (4/3796)

Long-term, low-dose Pb exposure in rats is associated with a significant decrease in transthyretin (TTR) concentrations in the CSF. Since CSF TTR, a primary carrier of thyroxine in brain, is produced and secreted by the choroid plexus, in vitro studies were conducted to test whether Pb exposure interferes with TTR production and/or secretion by the choroid plexus, leading to an impaired thyroxine transport at the blood-CSF barrier. Newly synthesized TTR molecules in the cultured choroidal epithelial cells were pulse-labeled with [35S]methionine. [35S]TTR in the cell lysates and culture media was immunoprecipitated and separated by SDS-PAGE, and quantitated by autoradiography and liquid scintillation counting. Pb treatment did not significantly alter the protein concentrations in the culture, but inhibited the synthesis of total [35S]TTR (cells + media), particularly during the later chase phase. Two-way ANOVA of the chase phase revealed that Pb exposure (30 microM) significantly suppressed the rate of secretion of [35S]TTR compared to the controls (p < 0.05). Accordingly, Pb treatment caused a retention of [35S]TTR by the cells. In a two-chamber transport system with a monolayer of epithelial barrier, Pb exposure (30 microM) reduced the initial release rate constant (kr) of [125I]T4 from the cell monolayer to the culture media and impeded the transepithelial transport of [125I]T4 from the basal to apical side of epithelial cells by 27%. Taken together, these in vitro data suggest that sequestration of Pb in the choroid plexus hinders the production and secretion of TTR by this tissue. Consequently, this may alter the transport of thyroxine across this blood-CSF barrier.  (+info)

Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. (5/3796)

Lactoferrin (Lf) is an iron-binding protein involved in host defense against infection and severe inflammation; it accumulates in the brain during neurodegenerative disorders. Before determining Lf function in brain tissue, we investigated its origin and demonstrate here that it crosses the blood-brain barrier. An in vitro model of the blood-brain barrier was used to examine the mechanism of Lf transport to the brain. We report that differentiated bovine brain capillary endothelial cells exhibited specific high (Kd = 37.5 nM; n = 90,000/cell) and low (Kd = 2 microM; n = 900,000 sites/cell) affinity binding sites. Only the latter were present on nondifferentiated cells. The surface-bound Lf was internalized only by the differentiated cell population leading to the conclusion that Lf receptors were acquired during cell differentiation. A specific unidirectional transport then occurred via a receptor-mediated process with no apparent intraendothelial degradation. We further report that iron may cross the bovine brain capillary endothelial cells as a complex with Lf. Finally, we show that the low density lipoprotein receptor-related protein might be involved in this process because its specific antagonist, the receptor-associated protein, inhibits 70% of Lf transport.  (+info)

Nonsaturable entry of neuropeptide Y into brain. (6/3796)

Neuropeptide Y (NPY) is found and is active both in the periphery and brain, but its crossing of the blood-brain barrier (BBB) in either direction has not been measured. We used multiple time-regression analysis to determine that radioactively labeled NPY injected intravenously entered the brain much faster than albumin, with an influx constant of 2.0 x 10(-4) ml. g. -1. min-1. However, this rate of entry was not significantly changed by injection of 10 microgram/mouse of excess NPY, by leptin, or by food deprivation. HPLC showed that most of the NPY entering the brain was intact, and capillary depletion with and without washout showed that the NPY did not remain bound to endothelial cells or associated with vascular elements. Perfusion in a blood-free solution eliminated binding to serum proteins as an explanation for the lack of saturation. Efflux of labeled NPY from the brain occurred at the same rate as albumin, reflecting the normal rate of reabsorption of cerebrospinal fluid. Thus NPY can readily enter the brain from blood by diffusion across the BBB.  (+info)

Selective delivery of herpes virus vectors to experimental brain tumors using RMP-7. (7/3796)

RMP-7, a bradykinin analog, has been shown to selectively open the blood-tumor barrier for the delivery of chemotherapeutic drugs to brain tumors. In contrast to bradykinin, RMP-7 has no hypotensive effects and has been approved for human use. This study was initiated to determine whether RMP-7 would open the blood-tumor barrier to virus vectors encoding tumor-killing genes in an experimental model. The herpes virus vector used, hrR3, which encodes virus thymidine kinase gene and the lacZ reporter gene, is defective in a gene encoding ribonucleotide reductase, replicates selectively in dividing tumor cells and not in postmitotic neural cells. It was determined that an optimum dose of RMP-7 (1.5-3.0 microg/kg over 10-15 minutes) enhanced viral delivery to brain tumors in rats bearing intracranial 9 L gliosarcomas when infused through the carotid artery immediately prior to virus vector application. Maximum expression of the lacZ reporter gene occurred at 3 days after intracarotid infusion. By 8 days, transgene expression was largely confined to tumor foci away from the main tumor mass. Viral delivery was essentially specific to tumor cells, with little transgene expression elsewhere in the brain. Minimal uptake and pathology was noted in the kidney, spleen, and liver. These findings indicate that intracarotid delivery of RMP-7 can augment the selective delivery of virus vectors to brain tumors in an experimental rat model, with the potential for application to human brain tumors.  (+info)

Orexin A but not orexin B rapidly enters brain from blood by simple diffusion. (8/3796)

We determined the ability of orexin A and orexin B, recently discovered endogenous appetite enhancers, to cross the blood-brain barrier (BBB) of mice. Multiple time-regression analysis showed that an i.v. bolus of 125I-orexin A rapidly entered the brain from the blood, with an influx rate (Ki = 2.5 +/- 0.3 x 10(-4) ml/g.min) many times faster than that of the 99mTc-albumin control. This relatively rapid rate of entry was not reduced by administration of excess orexin A (or leptin) or by fasting for 22 h, even when penetration into only the hypothalamus was measured. Lack of saturability also was shown by perfusion in blood-free buffer. HPLC revealed that most of the injected 125I-orexin A reached the brain as intact peptide. Capillary depletion studies showed that the administered peptide did not remain bound to the endothelial cells comprising the BBB but reached the brain parenchyma. Efflux of 125I-orexin A from the brain occurred at the same rate as 99mTc-albumin. The octanol/buffer partition coefficient of 0.232 showed that orexin A was highly lipophilic, whereas the value for orexin B was only 0.030. Orexin B, moreover, was rapidly degraded in blood, so no 125I-orexin B could be detected in intact form in brain when injected peripherally. Thus, although orexin B is rapidly metabolized in blood and has low lipophilicity, orexin A rapidly crosses the BBB from blood to reach brain tissue by the process of simple diffusion.  (+info)

*Blood-brain barrier

Blood-air barrier Blood-ocular barrier Blood-retinal barrier Blood-testis barrier Blood-thymus barrier Choroid plexus for blood ... A few regions in the brain, including the circumventricular organs, do not have a blood-brain barrier. The blood-brain barrier ... "History of Blood-Brain Barrier". Davis Lab. Retrieved 5 January 2015. "History of Blood-Brain Barrier". The Davis Lab. ... MS is a disease of the blood-brain barrier. The weakening of the blood-brain barrier may be a result of a disturbance in the ...

*Epileptic seizure

Failure of the blood-brain barrier may also be a causal mechanism. Focal seizures begin in one hemisphere of the brain while ... low blood sodium, hyperosmolar nonketotic hyperglycemia, high blood sodium, low blood calcium and high blood urea levels may ... Oby, E; Janigro, D (Nov 2006). "The blood-brain barrier and epilepsy". Epilepsia. 47 (11): 1761-74. doi:10.1111/j.1528- ... Normally brain electrical activity is non synchronous. In epileptic seizures, due to problems within the brain, a group of ...

*Glutamic acid

Smith, Quentin R. (April 2000). "Transport of glutamate and other amino acids at the blood-brain barrier". The Journal of ... Hawkins, Richard A. (September 2009). "The blood-brain barrier and glutamate". The American Journal of Clinical Nutrition. ... Glutamate does not easily pass the blood brain barrier, but, instead, is transported by a high-affinity transport system. It ... Malignant brain tumors known as glioma or glioblastoma exploit this phenomenon by using glutamate as an energy source, ...

*John Frank (epidemiologist)

Bilirubin beyond the blood-brain barrier. Pediatrics 1988; 81:304-15. 17. Frank JW. Causation revisited (Editorial). Journal of ... Occult blood screening for colorectal carcinoma: 3. Yield and costs. American Journal of Preventive Medicine 1985; 1(5):18-24. ... Occult blood screening for colorectal carcinoma: 1. The benefits. American Journal of Preventive Medicine 1985; 1(3):3-9. 6. ... Occult blood screening for colorectal carcinoma: 2. The risks. American Journal of Preventive Medicine 1985; 1(5):25-32. 7. ...

*CLDN12

Kniesel U, Wolburg H (2000). "Tight junctions of the blood-brain barrier". Cell. Mol. Neurobiol. 20 (1): 57-76. doi:10.1023/A: ... Tsukita S, Furuse M (2003). "Claudin-based barrier in simple and stratified cellular sheets". Curr. Opin. Cell Biol. 14 (5): ...

*Deltorphin I

Fiori A, Cardelli P, Negri L, Savi MR, Strom R, Erspamer V (August 1997). "Deltorphin transport across the blood-brain barrier ... May 1997). "Structure-activity relationships of a series of [D-Ala2]deltorphin I and II analogues; in vitro blood-brain barrier ... and on account of its unusually high blood-brain-barrier penetration rate, produces centrally-mediated analgesic effects in ...

*Glycosidic bond

"Biousian glycopeptides penetrate the blood-brain barrier". Tetrahedron: Asymmetry. Carbohydrate Science. Part 1. 16 (1): 65-75 ... "Improved bioavailability to the brain of glycosylated Met-enkephalin analogs". Brain Research. 881 (1): 37-46. doi:10.1016/ ...

*Mobile phone radiation and health

Stam R (2010). "Electromagnetic fields and the blood-brain barrier". Brain Res Rev (Review). 65 (1): 80-97. doi:10.1016/j. ... does not support the hypothesis that mobile phone radiation has an effect on the permeability of the blood-brain barrier. ... with the permittivity of the brain decreasing as one gets older and the higher relative volume of the exposed growing brain in ... Mobile phone use does not increase the risk of getting brain cancer or other head tumors. As the United States National Cancer ...

*Vascular recruitment

2009 Oct 23;105(9):860-8. What is the blood-brain barrier (not)? Bechmann I, Galea I, Perry VH. Trends Immunol. 2007 Jan;28(1): ... Vascular recruitment in the brain is thought to lead to new capillaries and increase the cerebral blood flow. The existence of ... That insulin can act in this way has been proposed based on increases in limb blood flow and skeletal muscle blood volume which ... Evidence that heterogeneity of cerebral blood flow does not involve vascular recruitment. Williams JL, Shea M, Jones SC. Am J ...

*Demyelinating disease

"Blood-Brain Barrier Disruption in Multiple Sclerosis". Sage Journals. Retrieved October 28, 2012. Abbott R, Silber E, Felber J ... "Spots" can occur as a result of changes in brain water content. Evoked potential is an electrical potential recorded from the ... deep brain thalamic stimulation (in the case of tremors). The progressive phase of MS appears driven by the innate immune ... depression and other diseases affecting the brain. It has also been used to study the metabolism of other organs such as ...

*ATP-binding cassette transporter

It is expressed primarily in the blood brain barrier and liver and is thought to be involved in protecting cells from toxins. ... "Challenges for blood-brain barrier (BBB) screening". Xenobiotica. 37 (10-11): 1135-51. doi:10.1080/00498250701570285. PMID ...

*CLDN14

Kniesel U, Wolburg H (2000). "Tight junctions of the blood-brain barrier". Cell. Mol. Neurobiol. 20 (1): 57-76. doi:10.1023/A: ... Sticky cells, blood vessels and cancer - the paradox of Claudin-14 - Marianne Baker, Cancer Research UK Science Update blog, 14 ... Tight junctions form continuous seals around cells and serve as a physical barrier to prevent solutes and water from passing ... There are also suggestions that CLDN14 plays a role in tumour angiogenesis (blood vessel formation), as deletion of a single ...

*CLDN5

Kniesel U, Wolburg H (2000). "Tight junctions of the blood-brain barrier". Cell. Mol. Neurobiol. 20 (1): 57-76. doi:10.1023/A: ... "Paracellular tightness and claudin-5 expression is increased in the BCEC/astrocyte blood-brain barrier model by increasing ... Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular ... Tsukita S, Furuse M (2002). "Claudin-based barrier in simple and stratified cellular sheets". Curr. Opin. Cell Biol. 14 (5): ...

*Discovery and development of tubulin inhibitors

Poor penetration through the blood-brain barrier. Because of numerous adverse effect and limitations in use, new drugs with ... From the patient, therapy is limited by poor absorption of a drug what lead to low concentration of active agent in the blood ... Some were found to have effect on lower blood sugar levels and others act as hemostatics. The most interesting thing was that ... A high number of white cells in the blood indicates leukemia, so a new anti-cancer drug had been discovered. These two ...

*S100B

Over the last decade, S100B has emerged as a candidate peripheral biomarker of blood-brain barrier (BBB) permeability and CNS ... Marchi N, Cavaglia M, Fazio V, Bhudia S, Hallene K, Janigro D (April 2004). "Peripheral markers of blood-brain barrier damage ... Czeisler BM, Janigro D (June 2006). "Reading and writing the blood-brain barrier: relevance to therapeutics". Recent patents on ... "Seizure-promoting effect of blood-brain barrier disruption". Epilepsia. 48 (4): 732-42. doi:10.1111/j.1528-1167.2007.00988.x. ...

*CLDN1

Kniesel U, Wolburg H (2000). "Tight junctions of the blood-brain barrier". Cell. Mol. Neurobiol. 20 (1): 57-76. doi:10.1023/A: ... Tsukita S, Furuse M (2002). "Claudin-based barrier in simple and stratified cellular sheets". Curr. Opin. Cell Biol. 14 (5): ... forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely ...

*CLDN10

Kniesel U, Wolburg H (2000). "Tight junctions of the blood-brain barrier". Cell. Mol. Neurobiol. 20 (1): 57-76. doi:10.1023/A: ... Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular ... Tsukita S, Furuse M (2003). "Claudin-based barrier in simple and stratified cellular sheets". Curr. Opin. Cell Biol. 14 (5): ...

*Zafirlukast

In vivo research indicates that zafirlukast has low blood-brain barrier penetration. The blood-brain barrier is a protective ... "The Blood-Brain Barrier in Neuroinflammatory Diseases". Pharmacological Reviews. 49 (2): 143-156. ISSN 0031-6997. Retrieved 7 ... The peak plasma level is the maximum concentration of zafirlukast in the blood. Zafirlukast is moderately distributed into the ... white blood cells that operate in the interstitial space of the lungs), and rarely in epithelial cells. CystLT1 is a receptor ...

*Flunarizine

It readily passes the blood-brain barrier. When given daily, a steady state is reached after five to eight weeks. ... Concentrations in the brain are about ten times higher than in the plasma. The substance is metabolised in the liver, mainly by ... Flunarizine is well absorbed (>80%) from the gut and reaches maximal blood plasma concentrations after two to four hours, with ...

*Abacavir

... can cross the blood-brain barrier. Abacavir is metabolized primarily through the enzymes alcohol dehydrogenase and ...

*CLDN19

Kniesel U, Wolburg H (2000). "Tight junctions of the blood-brain barrier". Cell. Mol. Neurobiol. 20 (1): 57-76. doi:10.1023/A: ... Tight junctions form barriers that control the passage of ions and molecules across an epithelial sheet and the movement of ... Tsukita S, Furuse M (2003). "Claudin-based barrier in simple and stratified cellular sheets". Curr. Opin. Cell Biol. 14 (5): ...

*Perivascular space

Another function is as an integral part of the blood-brain barrier (BBB). While the BBB is often described as the tight ... Bechmann, Ingo; Galea, Ian; Perry, V Hugh (2007). "What is the blood-brain barrier (not)?". Trends in Immunology. 28: 5-11. doi ... "Postulated role of vasoactive neuropeptide-related immunopathology of the blood brain barrier and Virchow-Robin spaces in the ... The pia mater is reflected from the surface of the brain onto the surface of blood vessels in the subarachnoid space. ...

*Ischemic cascade

Harmful chemicals damage the blood-brain barrier. Cerebral edema (swelling of the brain) occurs due to leakage of large ... molecules like albumins from blood vessels through the damaged blood brain barrier. These large molecules pull water into the ... The ischemic cascade usually goes on for two to three hours but can last for days, even after normal blood flow returns. A ... If and when the brain is reperfused, a number of factors lead to reperfusion injury. An inflammatory response is mounted, and ...

*Diphenoxylate

... brain, and spinal cord. Diphenoxylate itself crosses the blood-brain barrier. This being the case, this medication is ... which unlike the former two works exclusively in the intestines because it only crosses the blood-brain barrier in very small ...

*CLDN15

Kniesel U, Wolburg H (2000). "Tight junctions of the blood-brain barrier". Cell. Mol. Neurobiol. 20 (1): 57-76. doi:10.1023/A: ... Among its related pathways are Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling Pathways and Tight ... Tsukita S, Furuse M (2003). "Claudin-based barrier in simple and stratified cellular sheets". Curr. Opin. Cell Biol. 14 (5): ...

*Avid Radiopharmaceuticals

... would cross the blood-brain barrier and attach itself to amyloid protein deposits in the brain. Avid raised $500,000 from ... Of the patients included in the study, 29 who died had autopsies performed on their brains and in all but one the brain autopsy ... magnetic resonance imaging scans looking for brain shrinkage and PET scans looking at how glucose was used in the brain, had ... In 2002, a study performed in Sweden on Alzheimer's patients was able to detect the plaque in PET brain scans. Later studies on ...
TY - JOUR. T1 - Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin. T2 - An in vitro study. AU - Palmela, Inês. AU - Correia, Leonor. AU - Silva, Rui F M. AU - Sasaki, Hiroyuki. AU - Kim, Kwang Sik. AU - Brites, Dora. AU - Brito, Maria A.. PY - 2015. Y1 - 2015. N2 - Ursodeoxycholic acid and its main conjugate glycoursodeoxycholic acid are bile acids with neuroprotective properties. Our previous studies demonstrated their anti-apoptotic, anti-inflammatory and antioxidant properties in neural cells exposed to elevated levels of unconjugated bilirubin as in severe jaundice. In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular endothelial cells, unconjugated bilirubin has shown to induce caspase-3 activation and cell death, as well as interleukin-6 release and a loss of blood-brain barrier integrity. Here we tested the preventive and restorative effects of these ...
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One of the largest and fastest growing sectors in the global pharmaceutical industry is the development of treatments for diseases of the central nervous system. Unfortunately, current systemically administered medications do not achieve optimum therapeutic efficacy in the brain due to limitations in crossing the blood-brain barrier (BBB). Further research is needed to enhance the understanding of how and what molecules can pass through the BBB, and the creation of an in vitro BBB model is crucial to study the cellular constituents and the dynamic capabilities of the BBB that are difficult or nearly impossible to resolve in vivo. The most prevalent BBB model consists of a monolayer of endothelial cells grown on a porous membrane submerged in the wells of a multi-well plate. The large range of cell types available, cell culture variable set points (species, generation, co-culture setup), and system variable set points (membrane configuration, media composition) has resulted in an expansive number ...
Quantitative MRI reveals the elderly ischemic brain is susceptible to increased early blood-brain barrier permeability following tissue plasminogen activator related to claudin 5 and occludin disassembly
BACKGROUND: Blood brain barrier (BBB) disruption is accompanied by edema in the surrounding areas of the intracerebral hemorrhage (ICH). The aim of the study was to clarify the correlation between BBB breakdown and outcome in ICH. PATIENTS: Twenty-se
Results: A total of 212 patients, mean age (±SD) 69.5 years (±16.1), 102 (48%) male, had available MR before IV thrombolysis. Evidence of BBB leakage was present in 175 (80%) and 205 (94%) patients in the ischemic and nonischemic area, respectively. Lacunar infarcts (β = 0.17, p = 0.042) were associated with BBB leakage in the ischemic area, and brain atrophy was associated with BBB leakage in both ischemic (β = 0.20, p = 0.026) and nonischemic (β = 0.27, p = 0.001) areas. Increasing SVD grade was independently associated with BBB leakage in both ischemic (β = 0.26, p = 0.007) and nonischemic (β = 0.27, p = 0.003) area. ...
TY - JOUR. T1 - Penetration of small molecular weight substances through cultured bovine brain capillary endothelial cell monolayers. T2 - the early effects of cyclic adenosine 3,5‐monophosphate. AU - Deli, MA. AU - Dehouck, MP. AU - Abraham, CS. AU - Cecchelli, R.. AU - Joo, F.. PY - 1995/7/1. Y1 - 1995/7/1. N2 - Second messengers, such as cyclic adenosine 3,5‐monophosphate (cAMP), have been shown to take part in the regulation of blood‐brain barrier permeability. in the present study, elevation of cAMP levels decreased sucrose (mol. wt, 342) and inulin (mol. wt, 5000) permeability across monolayers of bovine brain capillary endothelial cells as early as 1 h after exposure. Since both tracers use predominantly a paracellular pathway, we assume that cAMP may increase the tightness of the tight junctions through protein phosphorylation.. AB - Second messengers, such as cyclic adenosine 3,5‐monophosphate (cAMP), have been shown to take part in the regulation of blood‐brain barrier ...
Our group recently verified that morphine pre-treatment facilitates doxorubicin delivery beyond the blood brain barrier (BBB) to the brain in the absence of signs of increased acute systemic toxicity in a rat model. Thus, it was plausible that morphine and other drugs as ondansetron inhibiting P-gp (MDR-1) localized on BBB, neurons and glial cells could increase the access of doxorubicin to the brain competing with the same efflux transporter, that very efficiently removes these drugs from the CNS. Thus, we explored the feasibility of active modification of the BBB protection, by using ondansetron pretreatment, to allow doxorubicin accumulation into the brain in an animal model. Rats were pretreated with different doses of intraperitoneal ondansetron before injection of doxorubicin (12 mg/kg). Quantitative analysis of doxorubicin was performed by mass spectrometry. Acute hearth and kidney damage was analyzed by measuring doxorubicin accumulation, LDH activity and malondialdehyde plasma levels. ...
Title: ABC Transporters and the Blood-Brain Barrier. VOLUME: 10 ISSUE: 12. Author(s):David J. Begley. Affiliation:Centre for Neuroscience Research, Kings College London, Hodgkin Building, Guys Campus, London SE1 1UL,UK.. Keywords:abc transporters, blood-brain barrier, blood-cerebrospinal fluid barrier. Abstract: The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) form a very effective barrier to the free diffusion of many polar solutes into the brain. Many metabolites that are polar have their brain entry facilitated by specific inwardly-directed transport mechanisms. In general the more lipid soluble a molecule or drug is, the more readily it will tend to partition into brain tissue. However, a very significant number of lipid soluble molecules, among them many useful therapeutic drugs have lower brain permeability than would be predicted from a determination of their lipid solubility. These molecules are substrates for the ABC efflux transporters which are present ...
The main pathophysiological factors of ICH include hematoma size and edema [38]. The formation of edema, which is mainly caused by disruption of the BBB following ICH, is associated with patient outcome. The BBB is composed of endothelial cells, tight junction proteins, astrocyte end-feet, and pericytes, which have the function of maintaining homeostasis of the neuro-parenchymal microenvironment [6]. Loss of BBB integrity is an important pathophysiological change that contributes to initiation of the inflammatory cascade, edema formation, and ultimately poor outcome [39]. In this study, the effect of MSCs on BBB leakage in ICH rats and relevant mechanisms were investigated after intravenous transplantation of MSCs.. Besides endothelial cell activation, vascular ONOO−, which is formed by NO and superoxide anion, is closely related to BBB leakage [37]. Studies have already shown that ONOO− alone is sufficient to induce BBB leakage, endothelial dysfunction, and neurodegeneration [40,41]. ...
Impaired blood-brain barrier function represents a significant component of hypoxic-ischemic brain injury in the perinatal period. Banks, W. A., Stonestreet, B. S. AntiCIL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus. mAb attenuate ischemia-reperfusionCrelated increases in BBB permeability in sheep fetuses (16). However, the role of IL-6 after injury in the immature brain has been studied much less extensively than those of IL-1and TNF-in the immature brain. We recently generated pharmacologic quantities of a highly selective, ovine-specific antiCIL-6 mAb and antiCIL-1mAb. The neutralizing abilities of these mAbs have previously been confirmed in ovine splenic mononuclear cell cultures (35). Moreover, we recently demonstrated that infusions of an antiCIL-1mAb result in the uptake of the antiCIL-1mAb into the brain and attenuate ischemia-reperfusionCrelated increases in BBB permeability in ovine fetal brain using the preclinical translational fetal sheep model ...
Dear Colleagues,. We would like to inform you that the registration and abstract submission for the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers is open till 31st of July and we are looking forward to your registration!. The symposium will be held September 13-15, 2017 in Kraków, Poland.. For more information please see: http://bbb.pan.olsztyn.pl/. The program covers all areas of blood-brain barriers research and reflects the latest developments in neurodegenerative diseases, membrane receptors and transporters, transcytosis regulators, epigenetic and transcriptional regulators, metabolic and nutrition regulation, in vivo and in vitro brain barriers models as well as the role of tight junctions and glycocalyx in blood brain barrier permeability. In addition, signaling pathways implicated in the development of neurological diseases and brain tumors are addressed.. We hope to meet you all in Kraków for this anniversary Blood-Brain Barriers event!. Best ...
Dear Colleagues,. We would like to inform you that the registration and abstract submission for the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers is open till 31st of July and we are looking forward to your registration!. The symposium will be held September 13-15, 2017 in Kraków, Poland.. For more information please see: http://bbb.pan.olsztyn.pl/. The program covers all areas of blood-brain barriers research and reflects the latest developments in neurodegenerative diseases, membrane receptors and transporters, transcytosis regulators, epigenetic and transcriptional regulators, metabolic and nutrition regulation, in vivo and in vitro brain barriers models as well as the role of tight junctions and glycocalyx in blood brain barrier permeability. In addition, signaling pathways implicated in the development of neurological diseases and brain tumors are addressed.. We hope to meet you all in Kraków for this anniversary Blood-Brain Barriers event!. Best ...
The effect of Aβ on BBB integrity has been studied in several cell culture models. Gonzalez-Velasquez et al showed that treatment of cultured human brain endothelial cells with 2.5 to 10 μmol/L Aβ40 triggered the TJ protein ZO-1 to retreat from the plasma membrane, which was accompanied by decreased transendothelial electric resistance.11 Marco and Skaper demonstrated that exposing rat brain endothelial cells to 20 μmol/L Aβ42 triggered ZO-1 and claudin-5 relocation from the plasma membrane, a decrease in occludin expression, and an increase in claudin-1 expression.21 Tai et al demonstrated that Aβ40 activated microtubule-associated protein kinase, which decreased occludin expression and increased permeability in human brain endothelial cell cultures, whereas claudin-5 and ZO-1 remained unchanged.22 Carrano et al analyzed postmortem CAA patient brain slices for TJ protein and observed a loss of occludin, claudin-5, and ZO-1 in brain microvessels.23 We show that hAβ40 decreased rat brain ...
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Increased permeability of the blood-brain barrier (BBB) is important in neurological disorders. Neuroinflammation is associated with increased BBB breakdown and brain injury. Tumor necrosis factor-alpha (TNF-a) is involved in BBB injury and edema formation through a mechanism involving matrix metalloproteinase (MMP) upregulation. There is emerging evidence indicating that cyclooxygenase (COX) inhibition limits BBB disruption following ischemic stroke and bacterial meningitis, but the mechanisms involved are not known. We used intracerebral injection of TNF-a to study the effect of COX inhibition on TNF-a-induced BBB breakdown, MMP expression/activity and oxidative stress. BBB disruption was evaluated by the uptake of 14C-sucrose into the brain and by magnetic resonance imaging (MRI) utilizing Gd-DTPA as a paramagnetic contrast agent. Using selective inhibitors of each COX isoform, we found that COX-1 activity is more important than COX-2 in BBB opening. TNF-a induced a significant upregulation ...
This unit describes various protocols for the in vivo quantitation of drug permeability across the rodent blood ‐ brain barrier
Reliable human in vitro blood-brain barrier (BBB) models suitable for high-throughput screening are urgently needed in early drug discovery and development for assessing the ability of promising bioactive compounds to overcome the BBB. To establish an improved human in vitro BBB model, we compared four currently available and well characterized immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, with respect to barrier tightness and paracellular permeability. Co-culture systems using immortalized human astrocytes (SVG-A cell line) and immortalized human pericytes (HBPCT cell line) were designed with the aim of positively influencing barrier tightness. Tight junction (TJ) formation was assessed by transendothelial electrical resistance (TEER) measurements using a conventional epithelial voltohmmeter (EVOM) and an automated CellZscope system which records TEER and cell layer capacitance (CCL) in real-time. Paracellular permeability was assessed using two fluorescent
TY - JOUR. T1 - Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations. AU - Brooks, Tracy A.. AU - Hawkins, Brian T.. AU - Huber, Jason D.. AU - Egleton, Richard D.. AU - Davis, Thomas P. PY - 2005/8. Y1 - 2005/8. N2 - The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study examined the effects of chronic inflammatory pain on the functional and molecular integrity of the BBB. Inflammatory pain was induced by injection of complete Freunds adjuvant (CFA) into the right plantar hindpaw in female Sprague-Dawley rats under halothane anesthesia; control animals were injected with saline. Edema and hyperalgesia were assessed by plethysmography and ...
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Modelling of the blood-brain barrier transport of morphine-3-glucuronidestudied using microdialysis in the rat: involvement ofprobenecid-sensitive transport. ...
The purpose of this study was to investigate whether a relationship exists between alterations of the blood-brain barrier (BBB) and the survival time of rats exposed to supralethal irradiation. BBB alterations were produced by injection of glycerol, mercuric chloride, or by lymphatic cervical blockade. Animals were subsequently exposed to a supralethal dose of radiation, and the survival times of various groups were compared. The production of BBB alterations prior to irradiation did not influence the survival time of rats after exposure to supralethal doses of radiation suggesting that BBB damage may bear no direct relationship to the survival time after radiation injury. (Author)
Blood-brain barrier (BBB) leakage plays a key role in cerebral ischemia-reperfusion injury. It is quite necessary to further explore the characteristic and mechanism of BBB leakage during stroke. We induced a focal cerebral ischemia model by transient middle cerebral artery occlusion in male rats for defining the time course of BBB permeability within 120 h following reperfusion and evaluate the specific role of tight junction (TJ) associated proteins claudin-5, occludin, and ZO-1 as well as protein kinase C delta (PKCδ) pathway in BBB leakage induced by reperfusion injury. We verified a bimodal increase in the permeability of the BBB following focal ischemia by Evans blue assay. Two peaks of BBB permeability appeared at 3 h and 72 h of reperfusion after 2 h focal ischemia, respectively. The leak at the endothelial cell was represented at the level of transmission electron microscopy. TTC staining results showed increased infarct size with time after cerebral ischemia reperfusion. The mRNA and ...
Although the mechanisms of action of antipsychotics (APs) on neuronal function are well understood, very little is known about their effects on cells of the blood-brain barrier (BBB); one function of which is to limit the access of these amphiphilic compounds to the central nervous system. To address this question we have investigated the cytological and functional effects of four APs: chlorpromazine (CLP), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ), at concentrations typical of high therapeutic dosage on a human brain microvascular endothelial cell (HBMEC) model of the BBB. At ~10 µM all four APs impaired the ability of HBMECs to reduce MTT which was followed by decreased Trypan blue exclusion and increased Lactate dehydrogenase release. These effects were associated with oxidative stress which was partly reversed by incubation in 10 mM glutathione. At their EC50 concentrations for MTT reduction, all four APs disrupted cellular ultrastructure and morphology. HAL, CPZ and CLZ ...
The blood-brain barrier (BBB) plays an important role in brain homeostasis. Hypoxia/ischemia constitutes an important stress factor involved in several neurological disorders by inducing the...
An intact blood-brain barrier and normal production, circulation, and absorption of cerebrospinal fluid are critical for normal brain function. Minor disruptions of barrier function are without clinical consequences. Major disruptions accompany most significant acute brain injuries. The anatomic location of the blood-brain barrier is the endothelial cells of arterioles, capillaries, veins, and the epithelial cell surface of the choroid plexus. However, endothelial cells require the presence of glial cells to maintain barrier function. During cardiopulmonary bypass, several factors may result in a temporary disruption of the barrier; the most important are systemic inflammatory response and focal ischemia due to emboli. Lacking a lymphatic system, the brain depends on the circulation of cerebrospinal fluid to remove the products of metabolism, and the circulation of cerebrospinal fluid depends on a vascular systolic pulse wave to drive this fluid antegrade along the brain paravascular spaces. Although it
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The blood-brain barrier is a physical and physiological barrier that protects the brain from toxic substances within the bloodstream and helps maintain brain homeostasis. It also represents the main obstacle in the treatment of many diseases of the central nervous system. Among the different approaches employed to overcome this barrier, the use of nanoparticles as a tool to enhance delivery of therapeutic molecules to the brain is particularly promising. There is special interest in the use of magnetic nanoparticles, as their physical characteristics endow them with additional potentially useful properties. Following systemic administration, a magnetic field applied externally can mediate the capacity of magnetic nanoparticles to permeate the blood-brain barrier. Meanwhile, thermal energy released by magnetic nanoparticles under the influence of radiofrequency radiation can modulate blood-brain barrier integrity, increasing its permeability. In this review, we present the strategies that use magnetic
Cardiac arrest and resuscitation in immature piglets result in a delayed increase in blood-brain barrier permeability. We tested the hypothesis that pretreatment with oxygen radical scavengers reduces postischemic permeability.. Permeability was assessed by measuring the plasma-to-brain transfer coefficient of the small amino acid, alpha-aminoisobutyric acid, in 2- to 3-week-old anesthetized piglets. Three groups were studied: (1) a nonischemic time control group (n = 5), (2) an ischemia group (n = 8) pretreated with 5 mL of polyethylene glycol vehicle, and (3) an ischemia group (n = 8) pretreated with polyethylene glycol conjugated to superoxide dismutase (10,000 U/kg) and to catalase (20,000 U/kg). The ischemia protocol consisted of 8 minutes of ventricular fibrillation, 6 minutes of cardiopulmonary resuscitation, defibrillation, and 4 hours of spontaneous circulation.. The mean +/- SEM of the transfer coefficient of alpha-aminoisobutyric acid in cerebrum was (in microL/g per minute): 1.54 +/- ...
Video articles in JoVE about animals domestic include Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay, Development of a Colloidal Gold-based Immunochromatographic Test Strip for Detection of Cetacean Myoglobin, Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids, Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells, Magnetic Stirrer Method for the Detection of Trichinella Larvae in Muscle Samples, Thermal Imaging to Study Stress Non-invasively in Unrestrained Birds, Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity (AIDN): A Translational Neuroscience Approach, Transabdominal Ultrasound for Pregnancy Diagnosis in Reeves Muntjac Deer, Spotting Cheetahs: Identifying Individuals by Their Footprints, The Bovine Lung in Biomedical Research: Visually Guided Bronchoscopy, Intrabronchial Inoculation and
phdthesis{2056153, abstract = {Several endogenous active peptides exist in the central nervous system (CNS), but the CNS drug development is hampered by the presence of the blood-brain barrier (BBB). The evaluation, modeling and understanding of the transport mechanisms at the BBB is very important for the development and optimization of potential CNS peptide drugs. Which techniques are used to quantitatively describe the BBB transport properties? Due to the multi-disciplinary complexity of the BBB research, several methodologies, each resulting in a specific parameter, are reported. Therefore, a coherent overview of the BBB-responses was described and a comprehensive database (Brainpeps{\textregistered}) constructed to collect the dispersed literature data. Chromatographic behavior of peptides on fused-core stationary phases? A representative peptide set was obtained via hierarchic clustering based on their structure properties. The chromatographic peptide interactions on the fused-core systems ...
Video articles in JoVE about membrane potentials include A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development, Electroretinogram Analysis of the Visual Response in Zebrafish Larvae, Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells, Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells, A Microfluidic System with Surface Patterning for Investigating Cavitation Bubble(s)-Cell Interaction and the Resultant Bioeffects at the Single-cell Level, Isolation of Type I and Type II Pericytes from Mouse Skeletal Muscles, Phase Behavior of Charged Vesicles Under Symmetric and Asymmetric Solution Conditions Monitored with Fluorescence Microscopy, From Fast Fluorescence Imaging to Molecular Diffusion Law on Live Cell Membranes in a Commercial Microscope,
A high-functioning blood brain barrier is obviously crucial to a high-functioning mind. Yet defense of the brain from inflammation and peripheral mayhem is not always effective. Molecules like alcohol easily pay off the guards and make the brain a pickled mess; it is no surprise when toxic substances such as ethanol and drugs cause problems in thinking and memory.. Yet domestic disturbances can also impact blood brain barrier function and thus brain function. For instance metabolic imbalances in glucose-both hyper- and hypoglycemia-are risk factors. Metabolic stress leads to immune dysfunction which may be one mechanism of action. (read Metabolic Syndrome and the Immunological Affair with the Blood-Brain Barrier in Frontiers in Immunology for an excellent instruction on the complex structure and function of blood-brain barrier systems).. Researchers are beginning to explore the effect of microbes.. They recently discovered that germ-free mice were different than control mice in this ...
The blood brain barrier is a network of tight junctions of endothelial cells in the central nervous system vessels. The cells are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains. These protective membranes serve to allow substances to cross into and out of the brain selectively. In a newborn, it takes approximately six weeks for the blood brain barrier to become formed.. Within the blood brain barrier there are circumventricular organs which include: a.) the Pineal body which secretes melatonin, associated with the normal twenty-four hour sleep/wake cycle; b.) the posterior Pituitary which releases neurohormones like oxytoxin (responsible for bonding) and vasopressin (which plays a key role in the regulation of water, glucose, and salts in the blood; c.) the Subfornical organ which is important for regulation of body fluids and; d.) the Vascular organ, a chemosensory area that detects peptides. Each of these organs is sensitive to toxicity. If any of ...
St. Marys College student Randy Larsen IV 19 spent the summer interning at the Womens Malignancies Branch of the National Cancer Institute. Under Senior Investigator Patricia Steeg, the lab focused on the mechanisms of how breast cancer metastasizes into the brain.. Larsens day-to-day mentor was researcher Lin Xiao. "Working with Dr. Xiao, my project focused on validating the use of induced pluripotent stem cells to create a more functionally accurate in vitro blood-brain barrier model," said Larsen. "In laymans terms, we cultured stem cells into brain cells - endothelial cells specifically - and found that when we used those new induced endothelial cells, our model behaved more like the in vivo brain compared to many currently used in vitro models.". "I had an amazing time working under Dr. Xiao and Dr. Steeg," said Larsen. "They were incredibly supportive, no matter how frustrating and time-consuming parts of my project were. Besides sharpening my lab skills, it was great to see what the ...
Hypoxic Stress Induced by Hydralazine Leads to a Loss of Blood-Brain Barrier Integrity and an Increase in Efflux Transporter Activity. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
In order to meet the high metabolic needs of the neurons "behind" the barrier in spite of its restrictive capacity, specific transport systems are selectively expressed in the CNS microvascular endothelial cells, which mediate the directed transport of nutrients from the blood into the CNS or the removal of toxic metabolites out of the CNS. Recent years have dramatically advanced our knowledge about the growth factors and their receptors specifically acting on the developing vascular endothelium including the CNS vasculature. Sci. Am. 255, 74-83. Janzer, R. , Raff, M. C. 1987, Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325, 253-257. Nag, S. 2003, The Blood-Brain Barrier, Humana Press, Totowa. , Helmchen, F. 2005, Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314-1318. Pardrige, W. M. 1993, The Blood-Brain Barrier: Cellular and Molecular Biology, Raven Press, New York. Paulson, O. , Moos, T. 1999, Blood-Brain ...
The role of nitric oxide (NO) in blood-brain barrier (BBB) or blood-spinal cord barriers (BSCB) disruption following central nervous system (CNS) injuries is not known in details. New data from our laboratory show that inhibition of neuronal nitric oxide synthase (NOS) expression by drugs or antibodies attenuate BBB and BSCB breakdown in CNS trauma or hyperthermia leading to neuroprotection. This review critically examines the role of NO in microvascular permeability disturbances following CNS injuries and other related neurological disorders. It appears that NO plays an important role in the breakdown of the BBB and BSCB function in CNS diseases. This indicates that NOS inhibitors have potential therapeutic value in CNS injuries or neurodegeneration in the near future.. ...
Date: November 19, 2014 Source: Karolinska Institutet Summary: Our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood, a new study in mice shows. The blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from…
Recent studies have shown that the blood-brain barrier is severely altered in epilepsy and that barrier dysfunction affects neuronal function and leads to seizures (Marchi et al., 2007a,b; Rigau et al., 2007; van Vliet et al., 2007; Tomkins et al., 2008; Kastanauskaite et al., 2009; Alonso-Nanclares and DeFelipe, 2014). One critical element of barrier dysfunction is barrier leakage, which was observed in animal seizure and epilepsy models as well as in epilepsy patients (Nitsch and Klatzo, 1983; Mihály and Bozóky, 1984; Cornford and Oldendorf, 1986; Horowitz et al., 1992; Padou et al., 1995). Our data from the present study are consistent with these observations. Several studies showed that blood-brain barrier leakage in epilepsy was restricted to anatomically specific brain regions and that these brain regions are often implicated in the development and propagation of seizures (Nitsch and Klatzo, 1983; Cornford et al., 1998). This suggests a connection between barrier leakage and seizures. ...
When ultrasound bursts are combined with a circulating microbubble agent, a temporary disruption in the blood-brain barrier (BBB) is induced that lasts for seve...
Objective: The normal blood brain barrier (BBB) is composed of tight junctions between endothelial cells and surrounding astrocyte foot processes. Breakdown of the physiological astrocyte-endothelial cell relationship occurs in adult metastatic and primary brain tumors. However, the astrocyte-endothelial cell relationship has not been studied in pediatric tumors. Materials and Methods: Utilizing specimens from cases of pilocytic astrocytoma (n = 5), medulloblastoma (n = 5), and low-grade diffuse astrocytoma (n = 1), immunofluorescence were performed using primary antibodies against CD31, glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQ4). Clinical, magnetic resonance imaging, operative, and histopathological findings were analyzed. Results: Strongly-enhancing areas of medulloblastoma exhibited complete BBB breakdown with sparse GFAP and AQ4 staining around CD31-positive vessels. Moderately enhancing regions of pilocytic astrocytomas exhibited regions of intact BBB and vasculature ...
The blood brain barrier (BBB) is a specialized barrier that renders the environment of the central nervous system (CNS) separate from other compartments of the body. The unique environment provided by the BBB enables the specialized activity of neurons; BBB breakdown is the result of pathologic conditions and leads to further neuronal dysfunction. The unique requirements of the CNS require the BBB to limit the free exchange of some solutes that would be freely exchanged through other anatomic compartments. The restriction of solute transport limits how fluids can transfer across the BBB.. The BBB is formed by endothelial cells that line cerebral micro vessels. 1 It restricts the entry of many substances dissolved in blood because of specialized tight junctions (TJ) between adjacent endothelial cells. BBB TJ are maintained by the interaction of specialized cytoskeleton and linking proteins not expressed in other endothelium, examples include : Claudins, occludins, and junctional adhesion ...
Associate Professor. One in four people worldwide - over 1.5 billion people - suffer from brain disorders, including depression, infection, trauma, stroke, seizures, dementia, and tumors. Despite this huge demand for treatments, delivery of drugs into the brain to treat these disorders is greatly impaired by the blood-brain barrier. The blood-brain barrier is the interface between blood and brain that controls what goes in and comes out of the brain. Anatomically, the blood-brain barrier is made of endothelial cells forming a complex vascular network that supplies the brain with oxygen and nutrients, and disposes of carbon dioxide and wastes. Recent studies show that the blood-brain barrier is affected by brain disorders and itself plays a role in causing brain disease. Therefore, understanding blood-brain barrier function is critical for devising new therapeutic strategies to enhance brain drug delivery, improve brain protection, and treat brain disorders. Currently, we study the role of the ...
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα). However, in vitro, activation of PDGF-CC by tPA is very inefficient and the mechanism of PDGF-CC activation in the NVU is not known. Here, we show that the integrin Mac-1, expressed on brain microglia/macrophages (denoted microglia throughout), acts together with the endocytic receptor LRP1 in the NVU to promote tPA-mediated activation of PDGF-CC. Mac-1-deficient mice (Mac-1 −/− ) are protected from tPA-induced BBB permeability but not from permeability induced ...
Cardiovascular Psychiatry and Neurology is a peer-reviewed, Open Access journal that publishes original pre-clinical/basic and clinical research on biological mechanisms of and treatments for co-occurring cardiovascular disorders and disorders of the central nervous system, including alterations in behavior, emotion, and cognition.
Hence, another aim of this thesis was to evaluate the potential of antibody-targeted polymersomes for the implementation of drug targeting strategies to the brain (section 3.3). For this purpose, the anti-human insulin receptor antibody 83-14 (83 14 mAb) was used as targeting vector because this antibody has been shown to undergo transcytosis in vivo upon binding to the insulin receptor with high affinity (Pardridge et al., 1995). Polymersomes based on poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) [PDMS-b-PMOXA] block copolymers were used in this study. Characterization of polymersomes confirmed their hollow sphere and vesicle-shaped morphology. Fluorescence correlation spectroscopy experiments showed the successful conjugation of the 83 14 mAb to the polymersomes. Flow cytometry analysis revealed binding and uptake of the 83 14 mAb conjugated polymersomes by brain capillary endothelial cells expressing the insulin receptor. Competitive uptake inhibition studies confirmed the ...
The blood-brain barrier at the interface between the brains blood vessels and nerve cells acts as a vital gatekeeper to the brain, allowing essential nutrients and fluids to pass into the central nervous system and the web of our brains neurons while keeping out harmful toxins and bacterial infection. Yet this barrier is so effective that it can also block the delivery of therapies for treating neurological diseases or brain injury.. A team at the Wyss Institute for Biologically Inspired Engineering, led by Wyss Institute Founding Director Donald Ingber, has advanced the Institutes Human Organs-on-Chips technology by developing a method for modeling the 3-D structure of the human blood-brain barrier inside a microfluidic device, which will help scientists study human neurovascular function and inflammation in vitro. The research is described online in the March 1 issue of PLOS ONE journal.. "The blood-brain barrier is the first line of defense against chemicals and molecules that could induce ...
The title of this blog is inspired by a structure I learned about in Anatomy. The blood brain barrier (BBB) is the vital gate keeper that protects the delicate neurons found in the Central Nervous System (CNS). The tight junctions of the capillaries around the entire perimeter of the CNS make those capillaries the least permeable capillaries in the body. All essential nutrients needed by the brains neurons, including oxygen, simply flow in, while most toxins are prohibited entrance. Although the BBB seems impregnable, it does allow some entrance of fat-soluble molecules, such as alcohol, nicotine, and anesthetic agents. I feel like the BBB accurately represents how I feel about own current aspirations. ...
Identification and characterisation of a new multidrug resistance protein at the blood brain barrier [Elektronische Ressource] / vorgelegt von Tanja Eisenblätter : TANJA EISENBLÄTTER IDENTIFICATION AND CHARACTERISATION OF A NEW MULTIDRUG RESISTANCE PROTEIN AT THE BLOOD-BRAIN BARRIER 2002 Biochemie IDENTIFICATION AND CHARACTERISATION OF A NEW MULTIDRUG RESISTANCE PROTEIN AT THE BLOOD-BRAIN BARRIER Inaugural-Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften im Fachbereich Chemie und Pharmazie der
Venkatakrishnan K, Tseng E, Nelson FR, Rollema H, French JL, Kaplan IV, Horner WE, Gibbs MA (August 2007). "Central nervous system pharmacokinetics of the Mdr1 P-glycoprotein substrate CP-615,003: intersite differences and implications for human receptor occupancy projections from cerebrospinal fluid exposures". Drug Metabolism and Disposition. 35 (8): 1341-9. doi:10.1124/dmd.106.013953. PMID 17470526 ...
TY - JOUR. T1 - Lidocaine turns the surface charge of biological membranes more positive and changes the permeability of blood-brain barrier culture models. AU - Santa-Maria, Ana R.. AU - Walter, Fruzsina R.. AU - Valkai, Sándor. AU - Brás, Ana Rita. AU - Mészáros, Mária. AU - Kincses, András. AU - Klepe, Adrián. AU - Gaspar, Diana. AU - Castanho, Miguel A.R.B.. AU - Zimányi, L.. AU - Dér, A.. AU - Deli, Mária A.. PY - 2019/9/1. Y1 - 2019/9/1. N2 - The surface charge of brain endothelial cells forming the blood-brain barrier (BBB) is highly negative due to phospholipids in the plasma membrane and the glycocalyx. This negative charge is an important element of the defense systems of the BBB. Lidocaine, a cationic and lipophilic molecule which has anaesthetic and antiarrhytmic properties, exerts its actions by interacting with lipid membranes. Lidocaine when administered intravenously acts on vascular endothelial cells, but its direct effect on brain endothelial cells has not yet been ...
Researcher have developed a new technique for using pulsed electric energy to open the blood-brain-barrier for treating brain cancer and neurological disorders.
Several studies suggest that cyclooxygenase (COX)-2 plays a pivotal role in the progression of ischemic brain damage. In the present study, we investigated the effects of selective inhibition of COX-2 with nimesulide (12 mg/kg) and selective inhibition of COX-1 with valeryl salicylate (VAS, 12-120 mg/kg) on prostaglandin E2 (PGE2) levels, myeloperoxidase (MPO) activity, Evans Blue (EB) extravasation and infarct volume in a standardized model of transient focal cerebral ischemia in the rat. Postischemic treatment with nimesulide markedly reduced the increase in PGE2 levels in the ischemic cerebral cortex 24 h after stroke and diminished infarct size by 48 % with respect to vehicle-treated animals after 3 days of reperfusion. Furthermore, nimesulide significantly attenuated the blood-brain barrier (BBB) damage and leukocyte infiltration (as measured by EB leakage and MPO activity, respectively) seen at 48 h after the initial ischemic episode. These studies provide the first experimental evidence ...
TY - JOUR. T1 - Targeting the PI3K pathway in the brain - Efficacy of a PI3K inhibitor optimized to cross the blood-brain barrier. AU - Salphati, Laurent. AU - Heffron, Timothy P.. AU - Alicke, Bruno. AU - Nishimura, Merry. AU - Barck, Kai. AU - Carano, Richard A.. AU - Cheong, Jonathan. AU - Edgar, Kyle A.. AU - Greve, Joan. AU - Kharbanda, Samir. AU - Koeppen, Hartmut. AU - Lau, Shari. AU - Lee, Leslie B.. AU - Pang, Jodie. AU - Plise, Emile G.. AU - Pokorny, Jenny L.. AU - Reslan, Hani Bou. AU - Sarkaria, Jann N. AU - Wallin, Jeffrey J.. AU - Zhang, Xiaolin. AU - Gould, Stephen E.. AU - Olivero, Alan G.. AU - Phillips, Heidi S.. PY - 2012/11/15. Y1 - 2012/11/15. N2 - Purpose: Glioblastoma (GBM), the most common primary brain tumor in adults, presents a high frequency of alteration in the PI3K pathway. Our objectives were to identify a dual PI3K/mTOR inhibitor optimized to cross the blood-brain barrier (BBB) and characterize its brain penetration, pathway modulation in the brain and efficacy ...
Researchers at the University of Wisconsin-Madison have made a critical breakthrough in unmasking the mysteries of the blood-brain barrier, which protects the brain from detriment, but also hinders it from receiving medical treatment. Through the use of stem cells, though, these researchers believe that they may have unlocked the potential of learning how to work beyond the limitations of the barrier in treating and curing brain damage.. The blood-brain barrier separates blood flow from the brains extracellular fluid and the central nervous system. The main purpose of the barrier is to protect the brain and its fluid from bacteria and disease; however, its main flaw is that it also disallows medicine to permeate the endothelial cells that comprise it. This becomes an issue as physicians and scientists have long tried to create and develop a cure to a number of brain diseases and injuries.. Now, though, through the use of stem cells, the Wisconsin researchers have replicated those endothelial ...
Glutaric acid (GA) is a dicarboxylic acid that accumulates in millimolar concentrations in glutaric acidemia I (GA-I), an inherited neurometabolic childhood disease characterized by extensive neurodegeneration. Vascular dysfunction is a common and early pathological feature in GA-I, although the underlying mechanisms remain unknown. In the present study, we have used a previously-validated rat model of GA-I to determine the effect of GA on the blood- brain barrier (BBB) and the neurovascular unit. Newborn rat pups received a single injection of GA (1 μmol/g) or vehicle into the cisterna magna. BBB permeability was analyzed at 14 and 30 days post injection (DPI) by assessing Evans blue (EB) and immunoglobulin G (IgG) extravasation. Blood vessels and microglia were labeled with tomato lectin. Characterization of EB positive cells was made by double labeling with antibodies to astrocyte and neuronal markers. Immunohistochemistry against aquaporin 4 (AQP4), β receptor of the platelet derived growth factor
The blood-brain barrier is located at the level of the brain blood capillaries. There are several components of the barrier.. Tight junctions. A key component of the blood-brain barrier is the tight junctions between endothelial cells in central nervous system capillary vessels that restricts the passage of solutes. At the interface between blood and brain, endothelial cells and associated astrocytes (type of glia) are stitched together by structures called "tight junctions." The tight junction is composed of smaller subunits, frequently dimers, that are transmembrane proteins such as occludin, claudins, junctional adhesion molecule (JAM), ESAM, and others. Each of these transmembrane proteins is anchored into the endothelial cells by another protein complex that includes zo-1 and associated proteins. The sealing together by tight junctions of the cells making up the walls of the vessels prevents water-soluble substances from freely passing between the cells and entering the fluid environment of ...
Acute stroke has a major effect on the cerebral vasculature with disruption of the neurovascular unit, leading to vasogenic edema. Breakdown of the blood-brain barrier (BBB) in ischemic stroke occurs in the early phases of ischemia, and is accentuated by IV treatment with recombinant tissue plasminogen activator, which increases the risk of hemorrhagic transformation and intracerebral hemorrhage.1,2 In a serendipitous observation using fluid-attenuated inversion recovery (FLAIR) MRI, gadolinium-DTPA enhancement of the CSF space overlying the ischemic tissue indicated greater stroke severity, increased age of the patient, and reperfusion injury. They called this phenomenon hyperintense acute reperfusion marker (HARM), and now Hitomi et al.3 have extended the original study to show enhancement of the structures in the eye. In addition to the endothelial blood-CNS barriers that maintain CNS homeostasis, regulate nutrition and detoxification, as well as immune cell trafficking into the brain and ...
Materials chosen to be part of the air barrier system should be chosen with care to avoid selecting materials that are too air-permeable, such as fiberboard, perlite board, and uncoated concrete block. The air permeance of a material is measured using ASTM E 2178 test protocol and reported in Litres/second per square meter at 75 Pa pressure (cfm/ft² at 0.3" w.g or 1.57 psf). The Canadian and IECC codes and ASHRAE 90.1 consider 0.02 L/s.m² 75 Pa (0.004 cfm/ft² 1.57 psf), which happens to be the air permeance of a sheet of ½" unpainted gypsum wall board, as the maximum allowable air leakage for a material that can be used as part of the air barrier system for the opaque enclosure; the same number is required by the Advanced Buildings Core Performance (New Buildings Institute), and ASHRAE SP 102 (Advanced Energy Design Guide: Small Office Buildings). The Air Barrier Association of America considers that number the industry standard for air barrier materials.. This maximum allowable air ...
Here, we are the first to show that microRNAs contribute to modulation of BBB function. We assessed microRNA expression in brain endothelial cells treated either with proinflammatory cytokines known to impair BBB function or with astrocyte-released factors that can strengthen BBB function. We found that while a large number of microRNAs were downregulated in brain endothelial cells with impaired BBB function, strengthening BBB function was generally associated with increased microRNA expression. Thus, we identified a microRNA signature that is central in the regulation of the balance between a tight and leaky BBB.. In our study, the expression of miR-125a-5p and many other microRNAs were regulated in human brain endothelial cells exposed to astrocyte factors. Importantly, brain capillaries are surrounded by and closely associated with the perivascular endfeet of astrocytes and there is now strong evidence that astrocytes can induce many BBB features, leading to tighter junctions (physical ...
The 20th congress of the Society for the study of blood-brain interfaces (SEISC) took place in Tours last week, on the topic "The Blood-Brain Barrier (BBB) in all its forms" (https://seisc.jimdo.com/congres-meeting-2017/). During two days, breakthroughs concerning several aspects of blood-brain interfaces were exposed through 11 presentations, dealing with the importance of the BBB in neurodegenerative diseases and in brain cancer, as well as the problematic of drug transport across the BBB.. The links between the BBB and neurodegenerative diseases were addressed in several presentations, for example the effect of ketones on the BBB, the cellular cholesterol homeostasis and β-amyloid peptide efflux at the level of the BBB in the frame of Alzheimers disease. BBB issues in cancerology were addressed in the context of high-grade glioma, with the modelization of the blood-tumor barrier using a human synergic approach. Moreover, modern methods for drug delivery across the BBB were presented. Some ...
As is well known, the blood-brain barrier is a strict checkpoint that prevents variety of drugs from reaching the brain. At the Massachusetts Eye and Ear/Harvard Medical School and Boston University researchers have developed a technique that enabled them to deliver glial derived neurotrophic factor (GDNF), a large protein being tested for treatment of Parkinsons disease, into the brains of mice. Currently GDNF is delivered by direct injection into the brain, a dangerous procedure that often leads to complications. The new technique relies on nasal mucosal grafting that is normally performed after minimally invasive brain tumor procedures to close the access route.. Nasal mucosa is considerably more lenient in letting molecules through than the blood-brain barrier, and so can act as a secret passage for drug delivery. When the researchers used this access point to deliver GDNF, they showed that the protein had an equivalent effect when compared to being delivered by a direct injection ...
Elodie obtained her Masters degree in Physiology, Physiopatholoy and Neurosciences at Lille 2 University in 2007. Then she joined the Blood-Brain Barrier Laboratory (LBHE, EA2465, Artois University) to prepare a PhD in Life Sciences that she defended in 2011: her project was dealing with the development of new in vitro blood-brain barrier (BBB) models for the study of cellular interactions in health and disease.. A first postdoctoral position in Mannheim Childrens Hospital (Germany, 2012-2013) allowed her to work on neuroblastoma brain metastasis. Back to France she worked on different topics using cellular models, from breast cancer brain metastasis (2014-2015) to the impact of ischemia on BBB cells (2016-2017), making her an expert in cell biology and complex in vitro systems.. Shes recently joined us as a study director!. ...
Implications of the blood-brain barrier and its manipulation , Implications of the blood-brain barrier and its manipulation , کتابخانه دیجیتال دانشگاه علوم پزشکی اصفهان
Despite effective systemic therapy, HIV-1 infection within the brain results in neuronal degradation and neurocognitive dysfunction. This neurocognitive dysfunction is worsened in the setting of opiate abuse. The central nervous system (CNS) is protected by the blood-brain barrier (BBB), a selective barrier regulating the passage of substances from peripheral circulation into the CNS. The BBB is composed of microvascular endothelial cells encased by basal lamina, pericytes, and perivascular astrocyte endfeet. Intracellular junctional complexes comprising of adherens and tight junctions are located between the endothelial cells and form tight barrier, preventing traffic of compounds between cells (paracellular flux). Clinical and in vitro data suggest that BBB integrity is compromised in HIV infection, which leads to a leaky barrier. Brain microvascular endothelial cells also express efflux transporters that are responsible for the extrusion of substances from the brain back into the blood. P
Interferons Interferons (IFN) act through cell receptors producing a variety of immu-nological and antiviral effects. Although the exact mechanism of action in multiple sclerosis is unknown, an anti-inflammatory effect may be the result of inhibition of interferon gamma, inhibition of T-cell activation, production of anti-inflammatory cytokines, reduced T-cell migration, decrease blood brain barrier permeability, or… Read More ». ...
Insightec has received approval from the US Food and Drug Administration (FDA) to initiate a study to evaluate the safety and feasibility of the Exablate Neuro for disrupting the blood brain barrier (BBB) in patients with Glioblastoma.. The blood brain barrier restricts the passage of substances from the bloodstream into the brain, protecting it from toxins. This barrier also prevents the effective delivery of agents, such as medications from reaching their target. In the current trial, the research team will inject a commonly used sonographic microbubble solution into the bloodstream of a patient with a malignant brain tumor. Ultrasound waves will then be delivered to oscillate the microbubbles causing temporary disruption of the blood brain barrier.. The trial will include up to 15 subjects with suspected glioblastoma who are scheduled to undergo tumor resection.. The Principal Investigator is Graeme F. Woodworth, MD, FACS, Associate Professor of Neurosurgery and Director of The Brain Tumor ...
Areas of Research: My research has focused on vascular transport and vascular permeability in health and disease. Recently we have been studying the blood brain barrier permeability to deliver drugs to tumors in the brain using a mouse model. ...
The complex interaction between an ultrasound-driven microbubble and an enclosing capillary microvessel is investigated by means of a coupled, multi-domain numerical model using the finite volume formulation. This system is of interest in the study of transient blood-brain barrier disruption (BBBD) for drug delivery applications. The compliant vessel structure is incorporated explicitly as a distinct domain described by a dedicated physical model. Red blood cells (RBCs) are taken into account as elastic solids in the blood plasma. We report the temporal and spatial development of transmural pressure (Ptm) and wall shear stress (WSS) at the luminal endothelial interface, both of which are candidates for the yet unknown mediator of BBBD. The explicit introduction of RBCs shapes the Ptm and WSS distributions and their derivatives markedly. While the peak values of these mechanical wall parameters are not affected considerably by the presence of RBCs, a pronounced increase in their spatial gradients ...
In vitro models of the blood-brain barrier (B-BB) generally utilise murine or porcine brain endothelium and rat astrocytes which are commonly grown in foetal calf serum supplemented conditions which modulate cell growth rates. Consequently, results gained from these experimental models can be difficult to extrapolate to the human in vivo situation since they are not of human origin. The proposed in vitro Transwell model of the B-BB is a multi-culture human cell system. It requires reconstruction of the human derived B-BB components in vitro (cerebral microvascular endothelial cells, astrocytes, and brain vascular pericytes) in a three-dimensional (3D) configuration based on Transwell filters. Different cell permutations (mono-, co-, and tri-cultivation) were investigated to find the most effective model in terms of tight junction resistance of the human cerebral microvascular endothelial cells. The B-BB model permutations comprised of human astrocytes (CC-2565 and SC-1810), human brain vascular ...
Brain metastasis is a common and severe complication arising in up to 40 % of cancer patients. The prognoses for patients with brain metastases are dismal, with a median treated survival of around 10 months. Treatment of brain metastases is mostly limited to surgery and radiotherapy, as an intact blood brain barrier (BBB) effectively protects smaller tumors from chemotherapeutic agents. This means that even if there would be effective chemotherapy treatment regimens for metastases elsewhere in the body, brain metastases would not be affected by such strategies until late stages of cancer development, when the BBB is disrupted. The prevalence of metastatic melanoma has been increasing steadily the last years accounting for 10 % of all brain metastatic cancers. Advanced stage melanoma patients are commonly treated with targeted inhibitors, such as vemurafenib (a small molecule inhibitor, tailored to have a higher affinity to the mutated BRAF kinase). However an intact BBB then prevents the brain ...
Blood-brain barrier (BBB) disruption has long been recognised as an important early feature of multiple sclerosis (MS) pathology. Traditionally, this has been seen as a by-product of the myelin-specific immune response. Here, we consider whether vascular changes instead play a central role in disease pathogenesis, rather than representing a secondary effect of neuroinflammation or neurodegeneration. Importantly, this is not necessarily mutually exclusive from current hypotheses. Vascular pathology in a genetically predisposed individual, influenced by environmental factors such as pathogens, hypovitaminosis D and smoking, may be a critical initiator of a series of events including hypoxia, protein deposition and immune cell egress that allows the development of a CNS-specific immune response and the classical pathological and clinical hallmarks of disease. We review the changes that occur in BBB function and cerebral perfusion in patients with MS and highlight genetic and environmental risk ...
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Multiple sclerosis (MS) is an autoimmune disease of the CNS characterized by disruption of the blood-brain barrier (BBB). This breach in CNS immune privilege allows undeterred trafficking of myelin-specific lymphocytes into the CNS where they induce demyelination. Although the mechanism of BBB compromise is not known, the chemokine CXCL12 has been implicated as a molecular component of the BBB whose pattern of expression is specifically altered during MS and which correlates with disease severity. The inflammatory cytokine IL-1β has recently been shown to contribute not only to BBB permeability but also to the development of IL-17-driven autoimmune responses. Using experimental autoimmune encephalomyelitis, the rodent model of MS, we demonstrate that IL-1β mediates pathologic relocation of CXCL12 during the induction phase of the disease, before the development of BBB disruption. We also show that CD4, CD8, and, surprisingly γδ T cells are all sources of IL-1β. In addition, γδ T cells are ...
Background: Polymerase δ-interacting protein 2 (Poldip2) is a multifunctional protein that regulates vascular extracellular matrix composition and matrix metalloproteinase (MMP) activity. The blood-brain barrier (BBB) is a dynamic system assembled by endothelial cells, basal lamina, and perivascular astrocytes, raising the possibility that Poldip2 may be involved in maintaining its structure. We investigated the role of Poldip2 in the late BBB permeability induced by cerebral ischemia. Methods: Transient middle cerebral artery occlusion (tMCAO) was induced in Poldip2 +/+ and Poldip2 +/- mice. The volume of the ischemic lesion was measured in triphenyltetrazolium chloride-stained sections. BBB breakdown was evaluated by Evans blue dye extravasation. Poldip2 protein expression was evaluated by western blotting. RT-PCR, zymography, and ELISAs were used to measure mRNA levels, activity, and protein levels of cytokines and MMPs. Cultured astrocytes were transfected with Poldip2 siRNA, and mRNA ...
Researchers from Harvard Medical School have identified a gene in mice, Mfsd2a, that may be responsible for limiting the blood-brain barriers permeability.
There are improvements of developments, drafts, and first larger download the blood brain barrier (bbb) elections effectively surveyed to the roll of being. It is sometimes a significant download the to be a period had safety and to address the volume, workflow and successful yarn that the true value has been into it. schools not are this download the blood brain as Whole, although it combines not geographically the team.
Epithelial and endothelial cells (EC) are building paracellular barriers which protect the tissue from the external and internal environment. The blood-brain barrier (BBB) consisting of EC, astrocyte end-feet, pericytes and the basal membrane is responsible for the protection and homeostasis of the brain parenchyma. In vitro BBB models are common tools to study the structure and function of the BBB at the cellular level. A considerable number of different in vitro BBB models have been established for research in different laboratories to date. Usually, the cells are obtained from bovine, porcine, rat or mouse brain tissue (discussed in detail in the review by Wilhelm et al. 1). Human tissue samples are available only in a restricted number of laboratories or companies 2,3. While primary cell preparations are time consuming and the EC cultures can differ from batch to batch, the establishment of immortalized EC lines is the focus of scientific interest. Here, we present a method for establishing ...
Luca Bors1, Ágnes Bajza1, Barbara Hutka1, László Dénes1, Krisztián Szigeti2, Nikolett Hegedűs2, Dávid Szöllősi2, Domokos Máthé2, Attila Csorba3 and Franciska Erdő1. Investigation of the impact of aging on blood-brain barrier function in rats - Does P-glycoprotein (P-gp) have any role in changing BBB permeability?. ...
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Sigma-Aldrich offers abstracts and full-text articles by [Alexander D Horsch, Jan Willem Dankbaar, Tom van Seeters, Joris M Niesten, Merel J A Luitse, Pieter C Vos, Irene C van der Schaaf, Geert-Jan Biessels, Yolanda van der Graaf, L Jaap Kappelle, Willem P Th M Mali, Birgitta K Velthuis].
Authors: Do, Tuan Minh , Dodacki, Agnès , Alata, Wael , Calon, Frederic , Nicolic, Sophie , Scherrmann, Jean-Michel , Farinotti, Robert , Bourasset, Fanchon Article Type: Research Article Abstract: The involvement of transporters located at the blood-brain barrier (BBB) has been suggested in the control of cerebral Aβ levels, and thereby in Alzheimers disease (AD). However, little is known about the regulation of these transporters at the BBB in animal models of AD. In this study, we investigated the BBB expression of Aβ influx (Rage) and efflux (Abcb1-Abcg2-Abcg4-Lrp-1) transporters and cholesterol transporter (Abca1) in 3-18-month-old 3xTg-AD and control mice. The age-dependent effect of BBB transporters regulation on the brain uptake clearance (Clup ) of [3 H]cholesterol and [3 H]Aβ1 - 40 was then evaluated in these mice, using the in …situ brain perfusion technique. Our data suggest that transgenes expression led to the BBB increase in Aβ influx receptor (Rage) and decrease in efflux ...
Pharmacokinetic parameters of human lymphoblastoid interferon (IFN-alpha) delivery to normal rat brain were examined. IFN-alpha concentrations in brain parenchyma could only be detected 120 min after its intravascular administration, and were 0.003% per gram of the administered dose. The mean cerebrovascular permeability-surface area (permeability x surface area) product to IFN, 120 min after infusion, was 0.35 x 10(-6) sec-1, which is not significantly different from zero. Neither i.v. nor intracarotid IFN-alpha administration significantly affected delivery to brain. Intrathecal administration of IFN-alpha, via the cisterna magna, resulted in undetectable concentrations in brain tissue and plasma at 30 and 60 min. However, osmotic blood-brain barrier opening significantly increased IFN-alpha delivery to brain after its carotid administration. A maximum concentration of 0.18% per gram of the total administered dose was achieved at 120 min, and the cerebrovascular permeability-surface area was ...
Wolfgang Wiedemair joined the group in October 2013 as a post-doctoral researcher. His research focus is on numerical modeling of biomedical processes such as oxygen transport and blood-brain barrier opening as well as the experimental validation of the latter. He is also interested in the physics of MRI and other medical imaging modalities.. Wolfgang finished his PhD at ETH Zurich under the guidance of Prof. Poulikakos in August 2013, developing a multi-domain modeling approach for the coupling of ultrasound and intravascular gas microbubbles, exploited in blood-brain barrier opening and other medical applications. The established computational platform allows for the assessment of mechanical conditions in microvessels caused by the microbubble dynamics. He received a Masters degree in Physics from Graz University of Technology for his research on non-invasive arterial spin labeling for lung perfusion quantification using MRI, conducted at the German Cancer Research Centre and the University ...
1989) Brain capillary 46,000 Dalton protein is cytoplasmic actin and is localized to endothelial plasma membrane. J. Cereb. Blood Flow Metab. 9, 675-680. 102. , Parkos, C. , et al. (2000) Tight junctions are membrane microdomains. J. Cell Sci. 113, 1771-1781. 103. , and Lisanti, M. P. (2001) The caveolin triad: caveolae biogenesis, cholesterol trafficking, and signal transduction. Cytokine Growth Factor Rev. 12, 41-51. 104. Madara, J. , and Kaoutzani, P. (1992) The movement of solutes and cells across tight junctions. 36. Stewart, P. , and Wiley, M. J. (1981) Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail-chick transplantation chimeras. Dev. Biol. 84, 183-192. 37. , and Risau, W. (1992) Expression of vascular endothelial growth-factor during embryonic angiogenesis and endothelial-cell differentiation. Development 114, 521-532. 38. , Escobedo, J. , and Williams, L. T. (1992) The fms-like tyrosine kinase, a ...
Its important for these leaks to be prevented or repaired, but creating openings in the blood-brain barrier could also be vital when it comes to treating brain diseases. At present, only 2% of brain disease drugs can actually get into the brain, which means brain tumour patients and people with neurological diseases have few options.. To give patients like these more options, work is going on to find ways to make the barrier more permeable. One method under investigation is a solution that removes water from the tissues around arteries leading into the brain. These cells shrivel up for a few hours, creating gaps though which the meds can travel unhindered until the cells return to their normal size. This method is still experimental, but its allowed chemotherapy drugs to reach brain tumours and there are big hopes for it.. ...
The blood-brain barrier (BBB) is a separation of circulating blood from the brain extracellular fluid (BECF) in the central nervous system (CNS). It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion of microscopic objects (e.g., bacteria) and large or hydrophilic…
The study, in mice and tissue samples, used a protein called TNF that can track down sites in the brain where cancer has spread by recognising a marker found only on tumour blood vessels.. The scientists, from the University of Oxford, found that TNF can home in on these sites and temporarily open the blood-brain barrier (BBB) allowing drugs to pass from the blood system into the tumour.. The BBB acts as a shield that prevents potentially dangerous particles such as bacteria entering the brain. But its this same shield that stops cancer drugs reaching tumours that have spread to the brain.. The TNF protein only broke down the BBB in the blood vessels that pass through the tumour, leaving the healthy parts of the brain undamaged by potentially toxic drugs. The research shows that when TNF is injected into the bloodstream the breast cancer drug herceptin (trastuzumab) which is not normally able to cross the BBB, can reach cancer cells in the brain.. As well as preventing drugs reaching tumours in ...
Martin Bauer, Kerstin Römermann, Rudolf Karch, Beatrix Wulkersdorfer, Johann Stanek, Cécile Philippe, Alexandra Maier-Salamon, Helmuth Haslacher, Christof Jungbauer, Wolfgang Wadsak, Walter Jäger, Wolfgang Löscher, Marcus Hacker, Markus Zeitlinger, Oliver Langer.Pilot PET study to assess the functional interplay between ABCB1 and ABCG2 at the human blood-brain barrier. Clin Pharmacol Ther 100(2):131-141 (2016) Kooperation Univ. Klinik für Klinische Pharmakologie mit Univ. Klinik für Radiologie und ...
Today the scientific journal Neuron published results on the Roche-designed Brain Shuttle technology that efficiently transfers investigational antibodies from the blood through the blood-brain barrier (BBB) into the brain in preclinical models. Roche Pharma Early Research and Development (pRED) scientists found that such enhanced transfer of antibodies through the BBB was associated with a marked improvement in amyloid reduction in the brain of a mouse model of Alzheimers disease.
Crossing the blood-brain barrier depends on the size of the particle, its lipid, or fat, content, and the electric charge on the particle. Zhang and colleagues built a particle that can pass through the barrier and reach tumors. To specifically target tumor cells they used chlorotoxin, a small peptide isolated from scorpion venom that many groups, including Zhangs, are exploring for its tumor-targeting abilities. On the nanoparticles surface Zhang placed a small fluorescent molecule for optical imaging, and binding sites that could be used for attaching other molecules ...
For a long time the brain has been considered an immune-privileged site due to a muted inflammatory response and the presence of protective brain barriers. It is now recognised that neuroinflammation may play an important role in almost all neurological disorders and that the brain barriers may be contributing through either normal immune signalling, or disruption of their basic physiological mechanisms. The distinction between normal function and dysfunction at the barriers is difficult to dissect, partly due to a lack of understanding of normal barrier function and partly because of physiological changes that occur as part of normal development and ageing. Brain barriers consist of a number of interacting structural and physiological elements including tight junctions between adjacent barrier cells and an array of influx and efflux transporters. Despite these protective mechanisms, the capacity for immune-surveillance of the brain is maintained, and there is evidence of inflammatory signalling at the
Hi How can i find if I have BBB leakage? doctor said he cannot determine it. I was stunned. I am asking because I always feel something is happening...
Abstract. The penetration of Cefuroxime (CXM), Ceftazidime (CTZ), Cefotaxime (CTX), Ceftizoxime (CZX), and Ceftriaxone (CTRX) across the blood-brain barrier was studied in 119 patients with or without meningitis after an intravenous injection of 2 grams. Cephalosporins were undetectable or their concentrations very low in the cerebrospinal fluid (CSF), when there was no inflammation in the meninges. On the contrary, the mean CSF concentrations of cephalosporins were 2.21-5.36 micrograms/ml and the CSF/serum ratios 3.73-31.80% in acute stage of purulent meningitis.. PMID:2582913. LymeMD thinks that Ceftriaxone penetrates the blood-brain barrier, presumably because it cures Meningitis and because it makes neuro-Lyme a little bit better. However they never realized that it is the Meningitis (inflammation of the capillary vessels that form the blood-brain-barrier) that opens the bbb. Meaning, without a damaged bbb, no penetration of Cephalosporins into the brain parenchyma.. Doctors keep clinging ...
Rising global prevalence of Parkinsons disease, meningitis, brain abscess, epilepsy, multiple sclerosis, encephalitis, Alzheimers disease and rapidly aging worlds population are some of the major drivers for the blood-brain barrier technologies market.
Most medicines cant get through the blood-brain barrier, but certain peptides in animal venoms can navigate across it to inflict damage. Now, researchers are capitalizing on venomous sneak attacks by developing a strategy based on a bee-venom peptide, apamin, to deliver medications to the brain. The researchers will present their work today at the 253rd National Meeting & Exposition of the American Chemical Society.
Glucose is the brains main energy source, and GLUT1 helps move it across the blood-brain barrier - a cellular layer that prevents entry of blood and pathogens into the brain. Previous research has shown diminished glucose uptake in the brain among individuals at genetic risk for Alzheimers, with a positive family history, and/or who develop the disease but show mild or no cognitive impairment.. In the new study, Zlokovics team used transgenic mice to show that GLUT1 is necessary to maintain proper brain capillary networks, blood flow and blood-brain barrier integrity. The team found that GLUT1 deficiency led to diminished glucose uptake into the brain as early as two weeks of age and, by six months of age, neuronal dysfunction, behavioral deficits, elevated levels of amyloid-beta peptide, behavioral changes and neurodegenerative changes. The team also found that GLUT1 deficiency in the endothelium - the inner lining of blood vessels - initiated breakdown of the blood-brain ...
Synonyms for blood-cerebrospinal fluid barrier in Free Thesaurus. Antonyms for blood-cerebrospinal fluid barrier. 1 word related to blood-brain barrier: barrier. What are synonyms for blood-cerebrospinal fluid barrier?
In order to adopt a general workflow for complex biological matrices with respect to a new blood-brain barrier (BBB) model, a micellar electrokinetic chromatography method has been developed. The cells forming the BBB have been cultivated in a special cell growth medium in which six drugs (acetaminophen, caffeine, carbamazepine, cimetidine, indometacin and propranolol) have been dissolved and tested for their penetration properties. The results showed good to very good accordance to the reference values. Samples were directly injected onto the capillary without any pretreatment (fused silica capillary, id: 50 μm, L: 48 cm, l: 40 cm). After method development, separations were carried out using a 60 mM borate buffer containing 200 mM of SDS at 30 kV, leading to an analysis time of less than 10 min. Between two runs the capillary was rinsed with a mixture of equal parts of running buffer and isopropanol (70% v/v), which proved to be very effective to remove matrix compounds. An appropriate choice ...
OBJECTIVES--To study the effect of bis (tributyl tin) oxide (TBTO) on permeability of the blood-brain barrier. METHODS--Electron microscopy and an x ray microanalyser with lanthanum chloride as a tracer were used, and blood tin concentrations were determined with an atomic absorption spectrophotometer. Adult male wistar rats received 0.05 ml/kg body weight of TBTO orally. RESULTS--A transient increase in paracellular permeability at the blood-brain barrier was found 2 h after the dose of TBTO. Electron dense lanthanum deposits penetrated tight junctions of the endothelia and permeated the subendothelial space. The x ray microprobe data showed an accumulation of TBTO at the tight junctions at 2 h. Leakage of tracer did not occur at 4 h, but oedematous changes in the surrounding glial cells were prominent between 4 and 8 h and had almost returned to normal by 24 h. By atomic absorption analysis, it was seen that blood tin concentrations rapidly increased at 1 h and rose to a maximum peak at 8 h, ...
Astragalus membranaceus is widely used to treat stroke and chronic debilitating diseases in China, but the mechanism has not been fully demonstrated to data. In the present study, we, using astragaloside IV, a purified extract from astragalus membranaceus, to a focal cerebral ischemia/reperfusion rat model, aimed to investigate the effect of astragaloside IV on the permeability of the blood-brain barrier since disruption of blood-brain barrier induced by ischemia/reperfusion leads to serious brain injuries. We found that astragaloside IV (10, 20 mg/kg) significantly attenuated the permeability of blood-brain barrier in comparison with vehicle group after ischemia/reperfusion assessed via Evans blue leakage (P,0.05). This was further confirmed by examination of blood-brain barrier permeability under the electron microscope, using lanthanum as a tracer of blood vessel permeability. Lanthanum was usually found within the blood vessel in sham group, rather than in perivascular tissues as shown in ...
Bradykinin as the major product of the contact-kinin system triggers inflammation and brain edema formation (for a comprehensive overview, see [2]). In this study, we aimed at targeting FXIIa, the very first step required for activation of this pathway in the plasma to alleviate pathological events leading to secondary injury after brain trauma.. Following brain trauma, bradykinin levels in the cerebrospinal fluid of patients are markedly elevated up to 48 h and decrease thereafter, reaching levels of the control group within 72 h after injury [19]. Similar to the human situation, bradykinin levels maximally increase within 2 h in the brain tissue of mice after experimentally induced focal brain trauma and then subsequently decline [7]. In accordance, we observed that plasma bradykinin levels increased twofold to threefold within 2 h after focal cortical injury in mice. As FXIIa activates plasma kallikrein, it is plausible to assume that posttraumatic bradykinin release is dependent on the ...
This study investigated the effects of 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetic acid (IOX3), a selective small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylases, on mouse brains subject to transient focal cerebral ischaemia. Male, 8- to 12-week-old C57/B6 mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) either immediately or 24 h after receiving IOX3. Mice receiving IOX3 at 20 mg/kg 24 h prior to the MCAO had better neuroscores and smaller blood-brain barrier (BBB) disruption and infarct volumes than mice receiving the vehicle, whereas those having IOX3 at 60 mg/kg showed no significant changes. IOX3 treatment immediately before MCAO was not neuroprotective. IOX3 up-regulated HIF-1α, and increased EPO expression in mouse brains. In an in vitro BBB model (RBE4 cell line), IOX3 up-regulated HIF-1α and delocalized ZO-1. Pre-treating IOX3 on RBE4 cells 24 h before oxygen-glucose deprivation had a protective effect on endothelial barrier ...
Disponible ahora en Iberlibro.com - Gastos de envío gratis - ISBN: 9787030305558 - paperback - Condición del libro: New - Paperback. Pub Date: 2011 04 of Pages: 200 in Publisher: Science Press drug application care (case) care series of secondary vocational education core curriculum textbooks one. Drug application care (Case) 13 chapters are drug application care Introduction. anti-microbial drugs. anticancer drugs. efferent nervous system drugs. local anesthetics. central nervous system drugs. antihistamines. role uterus drugs acting on the digestive system drugs acting on the respiratory system objects. diuret.
TY - GEN. T1 - Label-free in vivo optical micro-angiography imaging of cerebral capillary blood flow within meninges and cortex in mice with the skull left intact. AU - Yali, Jia. AU - Wang, Ruikang K.. PY - 2011. Y1 - 2011. N2 - Abnormal microcirculation within meninges is common in many neurological diseases. There is a need for an imaging method that is capable of visualizing functional meningeal microcirculations alone, preferably decoupled from the cortical blood flow. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ~2 mm, with an unprecedented imaging sensitivity to the blood flow at ~4 μm/s. In this study, we demonstrate the utility of ultra-high sensitive OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within meninges and cortex in mice with the cranium left intact. The results indicate that ...
Authors: Wardly DE.. Obstructive sleep apnea has been shown to increase intracranial pressure, and to be a secondary cause of intracranial hypertension. There are a few theories that attempt to explain this relationship, however there is little data, and even less recognition among physicians that this actually occurs. This paper discusses multiple pieces of data, from anatomical correlates to biochemical information involving neuro-excitotoxicity, as well as hematologic factors and issues surrounding brain edema and blood-brain barrier dysfunction. A complex paradigm for how obstructive sleep apnea may lead to increased intracranial pressure is thus proposed. In addition, suggestions are made for how obstructive sleep apnea must as a result be managed differently in the setting of idiopathic intracranial hypertension.. ...

Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: An in...Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: An in...

In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular ... In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular ... In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular ... In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular ...
more infohttps://jhu.pure.elsevier.com/en/publications/hydrophilic-bile-acids-protect-human-blood-brain-barrier-endothel-3

Download Blood Brain Barrier Permeability Changes After Subarachnoid Haemorrhage An Update Clinical Implications Experimental...Download Blood Brain Barrier Permeability Changes After Subarachnoid Haemorrhage An Update Clinical Implications Experimental...

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Development and application of an in vitro blood-brain barrier model to investigate intravenous immunoglobulin therapy for...Development and application of an in vitro blood-brain barrier model to investigate intravenous immunoglobulin therapy for...

Development and application of an in vitro blood-brain barrier model to investigate intravenous immunoglobulin therapy for ... Development and application of an in vitro blood-brain barrier model to investigate intravenous immunoglobulin therapy for ... medications do not achieve optimum therapeutic efficacy in the brain due to limitations in crossing the blood-brain barrier ( ... In conclusion, the optimized in vitro BBB model is a valuable tool for efficiently advancing the study of brain diseases and ...
more infohttp://udspace.udel.edu/handle/19716/13427?show=full

Quantitative MRI reveals the elderly ischemic brain is susceptible to increased early blood-brain barrier permeability...Quantitative MRI reveals the elderly ischemic brain is susceptible to increased early blood-brain barrier permeability...

Quantitative MRI reveals the elderly ischemic brain is susceptible to increased early blood-brain barrier permeability ... blood brain barrier; brain hematoma; brain ischemia; controlled study; disease exacerbation; drug megadose; male; middle ... Blood-Brain Barrier; Brain; Brain Ischemia; Fibrinolytic Agents; Infarction, Middle Cerebral Artery; Magnetic Resonance Imaging ... [email protected]: Quantitative MRI reveals the elderly ischemic brain is susceptible to increased early blood-brain barrier permeability ...
more infohttp://nparc.nrc-cnrc.gc.ca/eng/view/object/?id=ae12c4a7-5885-474d-9f42-8acdfa74a406

High Blood Pressure Effects on the Brain Barriers and Choroid Plexus SecretionHigh Blood Pressure Effects on the Brain Barriers and Choroid Plexus Secretion

... blood-cerebrospinal fluid barrier and blood brain barrier. The permeability of the brain barriers can be studied by using ... The high blood pressure produces a disruption of the blood brain barrier and blood to cerebrospinal fluid barrier that allows ... "Effect of Hypertension on the Integrity of Blood Brain and Blood CSF Barriers, Cerebral Blood Flow and CSF Secretion in the Rat ... B. J. Blyth, A. Farhavar and C. Gee, "Validation of Serum Markers for Blood-Brain Barrier Disruption in Traumatic Brain Injury ...
more infohttp://file.scirp.org/Html/9-2400107_17753.htm

Rabeprazole and Domperidone tablets - Zuche PharmaceuticalsRabeprazole and Domperidone tablets - Zuche Pharmaceuticals

Domperidone is a dopamine antagonist with anti-emetic properties domperidone does not readily cross the blood-brain barrier. ... which lies outside the blood-brain barrier in the area postrema. ...
more infohttp://zuchepharma.com/pharmaceuticals/rabeprazole-and-domperidone-tablets/

GastrointestinalGastrointestinal

... and diarrhea a loperamide cloridrato posologia diarrhea after taking bactrim does loperamide cross blood brain barrier giving ...
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An In-Depth Discussion on Domperidone | Bountiful FruitsAn In-Depth Discussion on Domperidone | Bountiful Fruits

... effects than older medications that were once used as a galactagogue because domperidone does not pass the blood-brain barrier ... These risks are related to the blood level of domperidone, and higher levels in the blood are associated with higher risks of ... Concurrent use of certain commonly used drugs, such as erythromycin, could raise blood levels of domperidone and further ... brain) tumor, and/or liver disease, with your healthcare provider. ...
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blood-brain barrier Archives - ExtremeTechblood-brain barrier Archives - ExtremeTech

Alarming levels of industrial pollution particles found in brains of city dwellers September 7, 2016 at 12:30 pm These ... ubiquitous reactive nanoparticles could be harmful to brain development, and even have an association with Alzheimers Disease. ...
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Neuro-Oncology Blood-Brain Barrier Program | OHSUNeuro-Oncology Blood-Brain Barrier Program | OHSU

... the blood-brain barrier, while also protecting cognitive functions. ... researchers works to meet the challenges of successfully treating people with brain tumors by outwitting the brains natural ... Background image: Neuro-Oncology Blood-Brain Barrier Program Neuro-Oncology Blood-Brain Barrier Program ... The OHSU Blood-Brain Barrier Program is a member of the OHSU Knight Cancer Institute and has strong affiliations with the ...
more infohttps://www.ohsu.edu/blood-brain-barrier

Crossing the Blood-Brain Barrier: Nanotechnology StrategiesCrossing the Blood-Brain Barrier: Nanotechnology Strategies

... providing a significant advantage over currently used drug delivery strategies for brain cancers and other CNS disorders. ... Nanotechnology may be the key to opening the gate of the blood brain-barrier, ... The previous theory that the blood-brain barrier (BBB) is a passive impermeable barrier that segregates blood and brain ... The blood-brain barrier (BBB) is meant to protect the brain from noxious agents; however, it also significantly hinders the ...
more infohttps://www.medscape.com/viewarticle/770396

blood brain barrier »blood brain barrier »

Blood-Brain Barrier. Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport ... Distribution of trivalent 51Cr in the rabbit; its possible use as an indicator of the blood-brain barrier. ... barrier for certain substances between the cerebral capillaries and the BRAIN tissue. ...
more infohttp://molecularstation.com/blood-brain-barrier/

Breaking through the Blood-Brain Barrier | GENBreaking through the Blood-Brain Barrier | GEN

... that may be responsible for limiting the blood-brain barriers permeability. ... Conversely, because researchers have begun to link blood-brain barrier degradation to several brain diseases, boosting Mfsd2a ( ... that may be responsible for limiting the blood-brain barriers permeability.. The barrier, which also operates in people, helps ... But because Mfsd2a has a human equivalent, blocking its activity in people could allow doctors to open the blood-brain barrier ...
more infohttps://genengnews.com/gen-news-highlights/breaking-through-the-blood-brain-barrier/81249872/

Blood-brain barrier - New World EncyclopediaBlood-brain barrier - New World Encyclopedia

The blood-brain barrier is located at the level of the brain blood capillaries. There are several components of the barrier. ... The blood-brain barrier (BBB) is a cellular and metabolic barrier located at the capillaries in the brain that alters ... the blood-brain barrier has broken down in a section of the brain or spinal cord, allowing white blood cells called T ... Enzymatic barrier. In addition to the above-mentioned passive components of the blood-brain barrier, there also are enzymes on ...
more infohttp://www.newworldencyclopedia.org/entry/Blood-brain_barrier

An Introduction to the Blood-Brain Barrier | SpringerLinkAn Introduction to the Blood-Brain Barrier | SpringerLink

... starts with a clear description of the key historical experiments which have led to the concept of this multi-faceted barrier ... An up-to-date basic introduction to the blood-brain barrier which ... An up-to-date basic introduction to the blood-brain barrier which starts with a clear description of the key historical ... Experimental Models in the Study of the Pathology of the Blood-Brain Barrier ...
more infohttps://link.springer.com/book/10.1007/978-1-349-11882-3

Core Concept: Circumventing the blood-brain barrier | PNASCore Concept: Circumventing the blood-brain barrier | PNAS

... efficient transporter present only at the blood-brain barrier," Shusta says. Using an in vitro blood-brain barrier model they ... Barriers to Discovery. Although attempts to penetrate the barrier have only recently gained steam, the blood-brain barrier ... A few groups are using ultrasound to temporarily open parts of the blood-brain barrier. "Over the last 20 years, blood-brain ... then the blood-brain barrier is its firewall. A specialized network of cells that lines the brains vascular system, the blood- ...
more infohttp://www.pnas.org/content/114/43/11261

blood-brain barrier | mBioblood-brain barrier | mBio

Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis at the Blood-Brain Barrier for Central Nervous System Entry ... Gamma Interferon Alters Junctional Integrity via Rho Kinase, Resulting in Blood-Brain Barrier Leakage in Experimental Viral ... These studies now provide insight into a previously unknown mechanism for how blood-brain barrier... ... we show that IFN-γ induces blood-brain barrier leakage. We show that IFN-γ promotes Rho kinase activity, resulting in actin ...
more infohttps://mbio.asm.org/keyword/blood-brain-barrier

LIBRIS - Blood-Brain Barrier Integrity...LIBRIS - Blood-Brain Barrier Integrity...

Blood-Brain Barrier Integrity in a Mouse Model of Alzheimers Disease With or Without Acute 3D6 Immunotherapy [Elektronisk ... Blood-Brain Barrier Integrity in a Mouse Model of Alzheimers Disease With or Without Acute 3D6 Immunotherapy [Elektronisk ... The blood-brain barrier (BBB) is suggested to be compromised in Alzheimers disease (AD). The concomitant presence of vascular ... After termination, fluorescent detection in brain and serum was used for the calculation of dextran brain-to-blood ...
more infohttp://libris.kb.se/bib/v4j8qtmpsnd8fw4l

Blood Brain Barrier (permeability)Blood Brain Barrier (permeability)

... vrijdag, 25 januari 2019 - Categorie: Onderzoeken. Bron: mdsafetech.org/blood-brain-barrier ... Blood-brain barrier permeability and nerve cell damage in rat brain 14 and 28 days after exposure to microwaves from GSM mobile ... Increased blood-brain barrier permeability in mammalian brain 7 days after exposure to the radiation from a GSM-900 mobile ... Permeability of the blood-brain barrier induced by 915 MHz electromagnetic radiation, continuous wave and modulated at 8, 16, ...
more infohttps://www.stopumts.nl/doc.php/Onderzoeken/11858/redir

blood-brain-barrier Archives | Bee Cultureblood-brain-barrier Archives | Bee Culture

... past the blood-brain barrier for drug delivery Credit: Giralt lab Most medicines cant get through the blood-brain barrier (BBB ...
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Blood-Brain Barrier Permeability Using Tracers and Immunohistochemistry | SpringerLinkBlood-Brain Barrier Permeability Using Tracers and Immunohistochemistry | SpringerLink

The first report of blood-brain barrier (BBB) permeability by Paul Ehrlich (1) involved the use of the exogenous tracer ... Nag S. (2003) Blood-Brain Barrier Permeability Using Tracers and Immunohistochemistry. In: Nag S. (eds) The Blood-Brain Barrier ... Nag, S. (1998) Blood-brain barrier permeability measured with histochemistry. In Introduction to the Blood-Brain Barrier. ... 1984) The protective influence of the locus ceruleus on the blood-brain barrier. Ann. Neurol. 15, 568-574.PubMedCrossRefGoogle ...
more infohttps://link.springer.com/protocol/10.1385%2F1-59259-419-0%3A133

Immune cells cross blood-brain barrier in multiple sclerosisImmune cells cross blood-brain barrier in multiple sclerosis

A new study in a mouse model of MS reveals two ways in which Th1 and Th17 immune cells cross the blood-barrier to attack the ... Alzheimers disease: Could a leaky blood-brain barrier be involved?. Learn how the blood-brain barrier was found to be leakier ... How do white blood cells penetrate the blood-brain barrier in MS? A new study investigates. ... One feature that can help the blood-brain barrier to restrict the movement of blood-borne cells, molecules, and ions into and ...
more infohttps://www.medicalnewstoday.com/articles/320148.php

Moving Past the Blood-Brain BarrierMoving Past the Blood-Brain Barrier

One reason? The blood-brain barrier (BBB): The protective endothelial membrane that guards the brain from potential invaders ... "We can use it to send growth factors or other deficient genes into the brain, for example. Really, being able to selectively ... In doing so, they have created tools that help further our understanding of difficult-to-reach brain circuitry as well as ... But AAV has been more challenging to harness for brain diseases and disorders because of the difficulty of crossing the BBB. ...
more infohttp://dana.org/News/Moving_Past_the_Blood-Brain_Barrier/

Breaching the Blood-Brain Barrier | The Scientist Magazine®Breaching the Blood-Brain Barrier | The Scientist Magazine®

... penetrating the blood-brain barrier for the first time. ... Researchers deliver cancer-fighting drugs to a patients brain ... blood-brain barrier. brain. brain cancer. brain tumor. cancer. chemotherapy. disease/medicine. drug development. ... Breaching the Blood-Brain Barrier. Researchers deliver cancer-fighting drugs to a patients brain via the bloodstream, ... FLICKR, JON OLAV EIKENESThe key to breaching the last great biochemical barricade in the body-the blood-brain barrier, a ...
more infohttps://www.the-scientist.com/the-nutshell/breaching-the-blood-brain-barrier-34516

Propping Open the Door to the Blood Brain BarrierPropping Open the Door to the Blood Brain Barrier

"Impact of initial vascular permeability and recovery speed of disrupted blood-brain barrier on nanodrug delivery into the brain ... Biophysics, Biophysical Society, Blood Brain Barrier (BBB), Ultrasound, Central Nervous System Diseases, ... of the blood brain barrier. However, finding a way to "prop the door open" to allow therapeutics to reach diseased tissue ... therapeutic agents such as recombinant proteins and gene medicines are not easily transported across the blood-brain barrier ( ...
more infohttp://www.newswise.com/articles/propping-open-the-door-to-the-blood-brain-barrier
  • We show that IFN-γ promotes Rho kinase activity, resulting in actin cytoskeletal contractions in the brain endothelium that lead to vascular junctional disorganization and cell-cell separations. (asm.org)
  • Drug distribution into the CSF is a function of drug transport across the choroid plexus, which forms the blood-CSF barrier, and not drug transport across the BBB, which is situated at the microvascular endothelium of brain. (nih.gov)
  • These agents may osmotically shrink barrier cells, possibly the vascular endothelium, and reversibly open spaces between them. (sciencemag.org)
  • however, it also significantly hinders the delivery of therapeutics to the brain. (medscape.com)
  • But the same system that protects the brain also stymies many therapeutics that could potentially treat disease. (pnas.org)
  • However, finding a way to "prop the door open" to allow therapeutics to reach diseased tissue without damaging normal brain tissue is the focus of a new study by a team of researchers at the Institute of Biomedical Engineering at National Taiwan University presenting at the 57th Annual Meeting of the Biophysical Society (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa. (newswise.com)
  • The team also used the spheroids to identify new brain-penetrant molecules, which could hold high potential for delivering therapeutics across the blood-brain barrier. (eurekalert.org)
  • Some strategies require multifunctional NPs combining controlled passage across the BBB with targeted delivery of the therapeutic cargo to the intended site of action in the brain. (medscape.com)
  • Although there are currently some limitations and concerns for the potential neurotoxicity of NPs, the future prospects for NP-based therapeutic delivery to the brain are excellent. (medscape.com)
  • Brain-penetrating antibodies and viruses could, for example, ferry therapeutic cargo across the border. (pnas.org)
  • Finding ways to stealthily shuttle drugs across the blood-brain barrier could have big therapeutic implications. (pnas.org)
  • The group is investigating the feasibility of using heparin, a common anticoagulant, to enhance the delivery of therapeutic macromolecules using ultrasound into the brain. (newswise.com)
  • Right now, 98 percent of small molecule drugs and 100 percent of large molecule drugs and antibodies can't get through the blood-brain barrier," said Chenghua Gu, Ph.D., associate professor of neurobiology at HMS and senior author of the study. (genengnews.com)
  • The blood-brain barrier also restricts the entry of antibodies that help to fight bacterial infections that do occur and makes it difficult for the delivery of water-soluble drugs that have been developed to treat diverse conditions. (newworldencyclopedia.org)
  • They found after 28 days of exposure that there were structural changes in the hippocampus and cortex, damage to the blood brain barrier, cellular edema and neuronal degeneration. (stopumts.nl)
  • Several strategies have been employed to deliver drugs across this barrier and some of these may do structural damage to the BBB by forcibly opening it to allow the uncontrolled passage of drugs. (medscape.com)
  • These so-called "tight junctions" are also found elsewhere in the circulatory system, but they are especially tight in the brain, restricting flow down to 10-15 angstroms ( 1 , 2 ). (pnas.org)
  • The goal of the Blood-Brain Barrier (BBB) Program is not only to prolong patients' length of survival, but also to improve the quality of their survival. (ohsu.edu)
  • The ideal method for transporting drugs across the BBB should be controlled and should not damage the barrier. (medscape.com)
  • Lipid-soluble nonelectrolytes damage the barrier irreversibly. (sciencemag.org)
  • An epileptic seizure, also known as an epileptic fit, is a brief episode of signs or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. (wikipedia.org)
  • Misconception 2 is that drug injected into the CSF compartment distributes to the inner parenchyma of brain. (nih.gov)
  • Drug penetration into brain parenchyma from the CSF is limited by diffusion and drug concentrations in brain decrease exponentially relative to the CSF concentration. (nih.gov)
  • Exposure to 900 MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats. (stopumts.nl)
  • It also works to control volume in the vertebrate brain, with its hard brain case, by maintaining constant levels of ions and peptides and limiting the movement of water and salts. (newworldencyclopedia.org)
  • While studying oxygen consumption in different organs, Ehrlich injected mice with an indicator dye that flowed throughout the body, staining all organs but one: the brain. (pnas.org)
  • A few regions in the brain, including the circumventricular organs, do not have a blood-brain barrier. (wikipedia.org)
  • A handful of drugs slip into the brain by passive diffusion-among them, antidepressants and medications for schizophrenia and epilepsy, along with caffeine, alcohol, and nicotine. (pnas.org)
  • Being able to open and close the blood-brain barrier also promises to benefit basic research, enabling scientists to investigate how abnormal barrier formation affects brain development and what the relationship may be between barrier deterioration and disease. (genengnews.com)
  • Reese, T. S., and Karnovsky, M. J. (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. (springer.com)
  • Structural and functional brain connectivity, synaptic activity, and information processing require highly coordinated signal transduction between different cell types within the neurovascular unit and intact blood-brain barrier (BBB) functions. (nih.gov)
  • After termination, fluorescent detection in brain and serum was used for the calculation of dextran brain-to-blood concentration ratios. (kb.se)
  • A few groups are using ultrasound to temporarily open parts of the blood-brain barrier. (pnas.org)
  • Breaching this barrier opens up a new frontier in treating brain disorders," Neal Kassell, chairman of the Focused Ultrasound Foundation, said in a press release . (the-scientist.com)
  • Focused ultrasound can be used to "open the door" of the blood brain barrier. (newswise.com)
  • "The fundamental hypothesis of this study was that blood vessel expansion and contraction induced by microbubble expansion and contraction can enhance the transport of intranasally-administered agents into the focused ultrasound-targeted brain region," ​ said Chen. (in-pharmatechnologist.com)
  • "Microbubbles are unique in that they expand and contract when sonicated by ultrasound, which pushes and pulls on the vessel wall and potentially contributes to the enhanced and localized brain drug delivery observed in this study," ​ Chen further explained. (in-pharmatechnologist.com)