Cuprizone: Copper chelator that inhibits monoamine oxidase and causes liver and brain damage.Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system.Corpus Callosum: Broad plate of dense myelinated fibers that reciprocally interconnect regions of the cortex in all lobes with corresponding regions of the opposite hemisphere. The corpus callosum is located deep in the longitudinal fissure.Myelin Sheath: The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.Oligodendroglia: A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.Monoamine Oxidase Inhibitors: A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414)Chelating Agents: Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.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.Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.Mice, Inbred C57BLAstrocytes: 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.Brain-Derived Neurotrophic Factor: A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994)Receptor, trkB: A protein-tyrosine kinase receptor that is specific for BRAIN-DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIN 3; neurotrophin 4 and neurotrophin 5. It is widely expressed in nervous tissue and plays a role in mediating the effects of neurotrophins on growth and differentiation of neuronal cells.Agenesis of Corpus Callosum: Birth defect that results in a partial or complete absence of the CORPUS CALLOSUM. It may be isolated or a part of a syndrome (e.g., AICARDI'S SYNDROME; ACROCALLOSAL SYNDROME; ANDERMANN SYNDROME; and HOLOPROSENCEPHALY). Clinical manifestations include neuromotor skill impairment and INTELLECTUAL DISABILITY of variable severity.Nerve Fibers, Myelinated: A class of nerve fibers as defined by their structure, specifically the nerve sheath arrangement. The AXONS of the myelinated nerve fibers are completely encased in a MYELIN SHEATH. They are fibers of relatively large and varied diameters. Their NEURAL CONDUCTION rates are faster than those of the unmyelinated nerve fibers (NERVE FIBERS, UNMYELINATED). Myelinated nerve fibers are present in somatic and autonomic nerves.Antigens, CD47: A ubiquitously expressed membrane glycoprotein. It interacts with a variety of INTEGRINS and mediates responses to EXTRACELLULAR MATRIX PROTEINS.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.Neural Cell Adhesion Molecule L1: A member of the immunoglobulin superfamily of neuronal cell adhesion molecules that is required for proper nervous system development. Neural cell adhesion molecule L1 consists of six Ig domains, five fibronectin domains, a transmembrane region and an intracellular domain. Two splicing variants are known: a neuronal form that contains a four-amino acid RSLE sequence in the cytoplasmic domain, and a non-neuronal form that lacks the RSLE sequence. Mutations in the L1 gene result in L1 disease. Neural cell adhesion molecule L1 is predominantly expressed during development in neurons and Schwann cells; involved in cell adhesion, neuronal migration, axonal growth and pathfinding, and myelination.Diffusion Tensor Imaging: The use of diffusion ANISOTROPY data from diffusion magnetic resonance imaging results to construct images based on the direction of the faster diffusing molecules.NorwayRhizoctonia: A mitosporic Ceratobasidiaceae fungal genus that is an important plant pathogen affecting potatoes and other plants. There are numerous teleomorphs.Giardiasis: An infection of the SMALL INTESTINE caused by the flagellated protozoan GIARDIA LAMBLIA. It is spread via contaminated food and water and by direct person-to-person contact.New JerseyExostoses: Benign hypertrophy that projects outward from the surface of bone, often containing a cartilaginous component.Mandibular DiseasesPalate, Hard: The anteriorly located rigid section of the PALATE.Electronic Mail: Messages between computer users via COMPUTER COMMUNICATION NETWORKS. This feature duplicates most of the features of paper mail, such as forwarding, multiple copies, and attachments of images and other file types, but with a speed advantage. The term also refers to an individual message sent in this way.Neuroradiography: Radiography of the central nervous system.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.United StatesPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease.Bibliometrics: The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)Biological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Audiovisual Aids: Auditory and visual instructional materials.Computer-Assisted Instruction: A self-learning technique, usually online, involving interaction of the student with programmed instructional materials.Food Inspection: Examination of foods to assure wholesome and clean products free from unsafe microbes or chemical contamination, natural or added deleterious substances, and decomposition during production, processing, packaging, etc.Structure Collapse: Failure in built environment with loss of functional integrity.BrazilTeaching: The educational process of instructing.FloridaOhioCimicidae: A family of wingless, blood-sucking insects of the suborder HETEROPTERA, including the bedbugs and related forms. Cimex (BEDBUGS), Heamatosiphon, and Oeciacus are medically important genera. (From Dorland, 28th ed)Bathing Beaches: Beaches, both natural and man-made, used for bathing and other activities.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Theilovirus: A species of CARDIOVIRUS which contains three strains: Theiler's murine encephalomyelitis virus, Vilyuisk human encephalomyelitis virus, and Rat encephalomyelitis virus.Libraries, Digital: Libraries in which a major proportion of the resources are available in machine-readable format, rather than on paper or MICROFORM.T-Lymphocytes, Regulatory: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.Forkhead Transcription Factors: A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.Interleukin-2 Receptor alpha Subunit: A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Checkpoint Kinase 2: Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.

Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. (1/102)

Metabolic insult results in apoptosis and depletion of mature oligodendrocytes during demyelination. To examine the role of insulin-like growth factor-1 (IGF-1) during acute demyelination and remyelination in the adult CNS, we exposed transgenic mice that continuously express IGF-1 (IGF-1 tg) to cuprizone intoxication. Demyelination was observed within the corpus callosum in both wild-type and IGF-1 tg mice 3 weeks after exposure to cuprizone. Wild-type mice showed significant apoptotic mature oligodendrocytes and a dramatic loss of these cells within the lesion that resulted in near complete depletion and demyelination by week 5. In contrast, the demyelinated corpus callosum of the IGF-1 tg mice was near full recovery by week 5. This rapid recovery was apparently caused by survival of the mature oligodendrocyte population because apoptosis was negligible, and by week 4, the mature oligodendrocyte population was completely restored. Furthermore, despite demyelination in both wild-type and IGF-1 tg mice, oligodendrocyte progenitors accumulated only in the absence of mature oligodendrocytes and failed to accumulate if the mature oligodendrocytes remained as demonstrated in the IGF-1 tg mice. These results suggest that IGF-1 may be important in preventing the depletion of mature oligodendrocytes in vivo and thus facilitates an early recovery from demyelination.  (+info)

Absence of macrophage-inflammatory protein-1alpha delays central nervous system demyelination in the presence of an intact blood-brain barrier. (2/102)

Chemokines are small chemotactic cytokines that modulate leukocyte recruitment and activation during inflammation. Here, we describe the role of macrophage inflammatory protein-1alpha (MIP-1alpha) during cuprizone intoxication, a model where demyelination of the CNS features a large accumulation of microglia/macrophage without T cell involvement or blood-brain barrier disruption. RNase protection assays showed that mRNA for numerous chemokines were up-regulated during cuprizone treatment in wild-type, C57BL/6 mice. RANTES, inflammatory protein-10, and monocyte chemoattractant protein-1 showed greatest expression with initiation of insult at 1-2 wk of treatment, whereas MIP-1alpha and beta increased later at 4-5 wk, coincident with peak demyelination and cellular accumulation. The function of MIP-1alpha during demyelination was tested in vivo by exposing MIP-1alpha knockout mice (MIP-1alpha(-/-)) to cuprizone and comparing pathology to wild-type mice. Demyelination at 3.5 wk of treatment was significantly decreased in MIP-1alpha(-/-) mice ( approximately 36% reduction), a result confirmed by morphology at the electron microscopic level. The delay in demyelination was correlated to apparent decreases in microglia/macrophage and astrocyte accumulation and in TNF-alpha protein levels. It was possible that larger effects of the MIP-1alpha deficiency were being masked by other redundant chemokines. Indeed, RNase protection assays revealed increased expression of several chemokine transcripts in both untreated and cuprizone-treated MIP-1alpha(-/-) mice. Nonetheless, despite this possible compensation, our studies show the importance of MIP-1alpha in demyelination in the CNS and highlight its effect, particularly on cellular recruitment and cytokine regulation.  (+info)

Interleukin-1beta promotes repair of the CNS. (3/102)

Interleukin-1beta (IL-1beta) is a proinflammatory cytokine associated with the pathophysiology of demyelinating disorders such as multiple sclerosis and viral infections of the CNS. However, we demonstrate here that IL-1beta appears to promote remyelination in the adult CNS. In IL-1beta(-/-) mice, acute demyelination progressed similarly to wild-type mice and showed parallel mature oligodendrocyte depletion, microglia-macrophage accumulation, and the appearance of oligodendrocyte precursors. In contrast, IL-1beta(-/-) mice failed to remyelinate properly, and this appeared to correlate with a lack of insulin-like growth factor-1 (IGF-1) production by microglia-macrophages and astrocytes and to a profound delay of precursors to differentiate into mature oligodendrocytes. Thus, IL-1beta may be crucial to the repair of the CNS, presumably through the induction of astrocyte and microglia-macrophage-derived IGF-1.  (+info)

The protective role of nitric oxide in a neurotoxicant-induced demyelinating model. (4/102)

Demyelination is often associated with acute inflammatory events involving the recruitment-activation of microglia/macrophage, astrocytes, and leukocytes. The ultimate role of inflammatory products in demyelinating disease and in the survival of oligodendrocytes, the myelin forming cells, is unresolved. The current study examines the role of inducible NO synthase (iNOS)-derived NO in a neurotoxicant-induced model of demyelination. NO levels were greatly elevated in the midline corpus callosum during demyelination in genetically intact C57BL/6 mice, and this NO was due solely to the induction of iNOS, as the correlates of NO were not found in mice lacking iNOS. C57BL/6 mice lacking iNOS exhibited more demyelination, but did not display an increased overall cellularity in the corpus callosum, attributable to an unimpeded microglia/macrophage presence. An enhanced course of pathology was noted in mice lacking iNOS. This was associated with a greater depletion of mature oligodendrocytes, most likely due to apoptosis of oligodendrocytes. Microglia and astrocytes did not undergo apoptosis during treatment. Our results suggest a moderately protective role for NO during acute inflammation-association demyelination.  (+info)

Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter. (5/102)

This study takes advantage of fibroblast growth factor 2 (FGF2) knock-out mice to determine the contribution of FGF2 to the regeneration of oligodendrocytes in the adult CNS. The role of FGF2 during spontaneous remyelination was examined using two complementary mouse models of experimental demyelination. The murine hepatitis virus strain A59 (MHV-A59) model produces focal areas of spinal cord demyelination with inflammation. The cuprizone neurotoxicant model causes extensive corpus callosum demyelination without a lymphocytic cell response. In both models, FGF2 expression is upregulated in areas of demyelination in wild-type mice. Surprisingly, in both models, oligodendrocyte repopulation of demyelinated white matter was significantly increased in FGF2 -/- mice compared with wild-type mice and even surpassed the oligodendrocyte density of nonlesioned mice. This dramatic result indicated that the absence of FGF2 promoted oligodendrocyte regeneration, possibly by enhancing oligodendrocyte progenitor proliferation and/or differentiation. FGF2 -/- and +/+ mice had similar oligodendrocyte progenitor densities in normal adult CNS, as well as similar progenitor proliferation and accumulation during demyelination. To directly analyze progenitor differentiation, glial cultures from spinal cords of wild-type mice undergoing remyelination after MHV-A59 demyelination were treated for 3 d with either exogenous FGF2 or an FGF2 neutralizing antibody. Elevating FGF2 favored progenitor proliferation, whereas attenuating endogenous FGF2 activity promoted the differentiation of progenitors into oligodendrocytes. These in vitro results are consistent with enhanced progenitor differentiation in FGF2 -/- mice. These studies demonstrate that the FGF2 genotype regulates oligodendrocyte regeneration and that FGF2 appears to inhibit oligodendrocyte lineage differentiation during remyelination.  (+info)

Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination. (6/102)

We examined the role of IGF signaling in the remyelination process by disrupting the gene encoding the type 1 IGF receptor (IGF1R) specifically in the mouse brain by Cre-mediated recombination and then exposing these mutants and normal siblings to cuprizone. This neurotoxicant induces a demyelinating lesion in the corpus callosum that is reversible on termination of the insult. Acute demyelination and oligodendrocyte depletion were the same in mutants and controls, but the mutants did not remyelinate adequately. We observed that oligodendrocyte progenitors did not accumulate, proliferate, or survive within the mutant mice, compared with wild type, indicating that signaling through the IGF1R plays a critical role in remyelination via effects on oligodendrocyte progenitors.  (+info)

Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination. (7/102)

To investigate insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression during experimental demyelination and myelin regeneration, young mice were fed cuprizone (( bis(cyclohexanone) oxaldihydrazone )). This copper-chelating agent produces demyelination in the corpus callosum and superior cerebellar peduncles, and when treatment is stopped, there is rapid remyelination. At intervals during cuprizone treatment and recovery, brain sections were hybridized with specific probes and immunostained with antibodies to determine the localization and relative amounts of IGF-I and IGF-I receptor mRNAs and peptides. In untreated littermates, IGF-I and IGF-I receptor mRNAs and peptides were not detected in white matter. In cuprizone-treated mice, high levels of both IGF-I mRNA and peptide were expressed by astrocytes in areas of myelin breakdown. Astrocyte IGF-I expression decreased rapidly during recovery and oligodendroglial expression of myelin-related genes increased. In severely demyelinated areas, immature oligodendroglia exhibited a transient increase in IGF-I receptor mRNA and peptide immunoreactivity during early recovery. This highly specific pattern of IGF-I induction in astrocytes during demyelination and the expression of the IGF-I receptor in regenerating oligodendrocytes during recovery suggest that IGF-I functions in the regulation of oligodendrocyte and myelin metabolism in vivo.  (+info)

Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. (8/102)

Tumor necrosis factor alpha (TNFalpha), a proinflammatory cytokine, was shown previously to promote remyelination and oligodendrocyte precursor proliferation in a murine model for demyelination and remyelination. We used Affymetrix microarrays in this study to identify (1) changes in gene expression that accompany demyelination versus remyelination and (2) changes in gene expression during the successful remyelination of wild-type mice versus the unsuccessful attempts in mice lacking TNFalpha. Alterations in inflammatory genes represented the most prominent changes, with major histocompatibility complex (MHC) genes dramatically enhanced in microglia and astrocytes during demyelination, remyelination, and as a consequence of TNFalpha stimulation. Studies to examine the roles of these genes in remyelination were then performed using mice lacking specific genes identified by the microarray. Analysis of MHC-II-null mice showed delayed remyelination and regeneration of oligodendrocytes, whereas removal of MHC-I had little effect. These data point to the induction of MHC-II by TNFalpha as an important regulatory event in remyelination and emphasize the active inflammatory response in regeneration after pathology in the brain.  (+info)

The cuprizone model is a well-established and investigated paradigm to study demyelination and remyelination in rodents. Cuprizone is usually administrated by mixing in the powdered or pelleted rodent chow. However, since cuprizone is sensitive to the environment and the consumption of it varies between different animals, the major issue is the discrepancy in demyelination of the animals. This study reports the development of the cuprizone model by gavage administrations in mice. Following testing a series of doses of cuprizone, 400 mg/kg/day was found to be the best dosage to induce dramatic and consistent demyelination after 5 weeks of administration; while remyelination quickly occurred after 9 days of cuprizone withdrawal ...
Previous studies have clearly demonstrated the indispensable role of IL-17 in the induction and pathogenesis of EAE, which resembles the pattern I and II MS lesions driven by T cell-mediated autoimmune inflammatory response. In this study, we show for the first time that IL-17-mediated signaling plays a critical role in cuprizone-induced demyelination, which shares similarities with pattern III MS lesions associated with apoptosis of myelin-forming oligodendrocytes and pronounced loss of oligodendrocytes. Interestingly, mice deficient in IL-17A, IL-17RC, and adaptor protein Act1 (of IL-17R) displayed diminished demyelination, microglial accumulation, and leukocyte infiltration compared with that in wild-type mice in response to cuprizone. Importantly, astrocytes are highly responsive to IL-17 in vitro, and selective deletion of Act1 in astrocytes ameliorated cuprizone-induced demyelination. Together, these results suggest that IL-17-mediated signaling in astrocytes contributes to the ...
Figure 1. BM-derived cells are recruited in a CCR2-dependent manner into demyelinating sites of the CNS in the cuprizone model. (A) A Busulfan/Cyclophosphamide chemotherapy regimen was used to prepare WT mice to receive the injection of BM cells from GFP+/− mice. 6 wk after transplantation, 0.2% Cuprizone was added to the diet for up to 6 wk. Mice were sacrificed after 2, 3, 4, 5, and 6 wk on a cuprizone-supplemented diet. Another group was sacrificed 2 wk after removing cuprizone from the diet to allow remyelination. (B) Flow cytometry analysis of GFP expression in circulating monocytes of WT mice, GFP+/− mice, chimeric GFP → WT mice, and and CCR2−/− → WT mice. (C) GFP+ cells were counted with a stereologic apparatus. Reported is the total number of GFP+ cells per slice counted per animal. (D-F) Representative confocal images of GFP+ cells (green) and immunoreactive Iba1+ cells (red) in the hippocampus and corpus callosum of chimeric mice either untreated (D) or after 5 wk of ...
Neurotrophin signaling impacts development and health of oligodendrocyte lineage cells. Brain-derived neurotrophic factor (BDNF) has been of particular interest. BDNF increases DNA synthesis in cultured basal forebrain oligodendrocyte progenitors (Vant Veer et al., 2009) and enhances oligodendrocyte differentiation to myelin protein-expressing cells (Du et al., 2006). Moreover, BDNF deficient mice exhibit deficits in progenitors and myelin protein expression (Vondran et al., 2010) and the conditional knock-out of the BDNF receptor TrkB from mature, MBP+ oligodendrocytes results in reduced myelin thickness in both the spinal cord and the corpus callosum (Wong et al., 2013).. These effects may be relevant to in vivo demyelination. For example, in the cuprizone demyelination model expression of BDNF is decreased in the corpus callosum, and animals deficient in BDNF exhibit a more severe loss of myelin protein in the lesioned corpus callosum than do their wild-type littermates (VonDran et al., ...
Baxi, E.G., DeBruin, J., Jin, J., Strasburger, H.J., Smith, M.D., Orthmann-Murphy, J.L., Schott, J.T., Fairchild, A.N., Bergles, D.E., and Calabresi, P.A. (2017). Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination. Glia 65, 2087-2098.. Kim, J., Hughes, E.G., Shetty, A.S., Arlotta, P., Goff, L.A., Bergles, D.E., and Brown, S.P. (2017). Changes in the Excitability of Neocortical Neurons in a Mouse Model of Amyotrophic Lateral Sclerosis Are Not Specific to Corticospinal Neurons and Are Modulated by Advancing Disease. J. Neurosci. 37, 9037-9053.. Assinck, P., Duncan, G.J., Plemel, J.R., Lee, M.J., Stratton, J.A., Manesh, S.B., Liu, J., Ramer, L.M., Kang, S.H., Bergles, D.E., et al. (2017). Myelinogenic Plasticity of Oligodendrocyte Precursor Cells following Spinal Cord Contusion Injury. J. Neurosci. 37, 8635-8654.. Langseth, A.J., Kim, J., Ugolino, J.E., Shah, Y., Hwang, H.-Y., Wang, J., Bergles, D.E., and Brown, S.P. (2017). ...
The present study aimed to orally deliver methylthioadenosine (MTA) to the brain employing solid lipid nanoparticles (SLNs) for the management of neurological conditions like multiple sclerosis. The stearic acid-based SLNs were below 100 nm with almost neutral zeta potential and offered higher drug entrapment and drug loading. Cuprizone-induced demyelination model in mice was employed to mimic the multiple sclerosis-like conditions. It was observed that the MTA-loaded SLNs were able to maintain the normal metabolism, locomotor activity, motor coordination, balancing, and grip strength of the rodents in substantially superior ways vis-à-vis plain MTA. Histopathological studies of the corpus callosum and its subsequent staining with myelin staining dye luxol fast blue proved the potential of MTA-loaded SLNs in the remyelination of neurons. The pharmacokinetic studies provided the evidences for improved bioavailability and enhanced bioresidence supporting the pharmacodynamic findings. The studies ...
Charles River conducts studies in both inflammation-induced and demyelination in vivo MS models (cuprizone model and EAE model) to test the efficacy of novel therapeutics.
Walsh DA, Merson TD, Landman KA, Hughes BD. (2016) Evidence for Cooperative Selection of Axons for Myelination by Adjacent Oligodendrocytes in the Optic Nerve. PLoS ONE 11 (11): e0165673. Walsh DA, Röth PT, Holmes WR, Landman KA, Merson TD, Hughes BD. (2016) Is cell migration or proliferation dominant in the formation of linear arrays of oligodendrocytes? J Theor Biol 406:17-30.. Huang L, Merson TD, Bourne JA. (2016) In vivo whole brain, cellular and molecular imaging in nonhuman primate models of neuropathology. Neurosci Biobehav Rev 66:104-118.. Mitew S, Xing YL, Merson TD. (2016) Axonal activity-dependent myelination in development: insights for myelin repair. J Chem Neuroanat pii: S0891-0618(16)30029-1. Xing YL, Röth PT, Stratton JA, Chuang BHA, Danne J, Ellis SL, Ng SW, Kilpatrick TJ, Merson TD. (2014) Adult neural precursor cells from the subventricular zone contribute significantly to oligodendrocyte regeneration and remyelination. J Neurosci 34:14128-46.. Merson TD, Bourne JA. (2014) ...
Walsh DA, Merson TD, Landman KA, Hughes BD. (2016) Evidence for Cooperative Selection of Axons for Myelination by Adjacent Oligodendrocytes in the Optic Nerve. PLoS ONE 11 (11): e0165673. Walsh DA, Röth PT, Holmes WR, Landman KA, Merson TD, Hughes BD. (2016) Is cell migration or proliferation dominant in the formation of linear arrays of oligodendrocytes? J Theor Biol 406:17-30.. Huang L, Merson TD, Bourne JA. (2016) In vivo whole brain, cellular and molecular imaging in nonhuman primate models of neuropathology. Neurosci Biobehav Rev 66:104-118.. Mitew S, Xing YL, Merson TD. (2016) Axonal activity-dependent myelination in development: insights for myelin repair. J Chem Neuroanat pii: S0891-0618(16)30029-1. Xing YL, Röth PT, Stratton JA, Chuang BHA, Danne J, Ellis SL, Ng SW, Kilpatrick TJ, Merson TD. (2014) Adult neural precursor cells from the subventricular zone contribute significantly to oligodendrocyte regeneration and remyelination. J Neurosci 34:14128-46.. Merson TD, Bourne JA. (2014) ...
Radiotherapy is the mainstay of treatment after surgery for high-grade gliomas and is usually well tolerated. Radiation toxicity in the brain is usually classified according to the timing of side effects in relation to treatment, as either acute (during radiotherapy), early delayed (within 12 weeks of radiotherapy) or late delayed (months to years after radiotherapy). We report two cases of young women who developed severe acute demyelination within 4 months of radiotherapy for glioma, one of whom had a previous history of transverse myelitis. Both improved with corticosteroids and remain in tumour remission. These cases emphasise the importance of careful discussion with patients before starting radiotherapy if there is a previous history of central nervous system demyelination or multiple white matter lesions on MRI. ...
High resolution diffusion tensor images of the mouse brain were acquired using the pulsed gradient spin echo sequence and the oscillating gradient spin echo sequence. The oscillating gradient spin echo tensor images demonstrated frequency-dependent changes in diffusion measurements, including apparent diffusion coefficient and fractional anisotropy, in major brain structures. Maps of the rate of change in apparent diffusion coefficient with oscillating gradient frequency revealed novel tissue contrast in the mouse hippocampus, cerebellum, and cerebral cortex. The observed frequency-dependent contrasts resembled neuronal soma-specific Nissl staining and nuclei-specific 4,6-diamidino-2-phenylindole (DAPI) staining in the mouse brain, which suggests that the contrasts might be related to key features of cytoarchitecture in the brain. In the mouse cuprizone model, oscillating gradient spin echo-based diffusion MRI revealed significantly higher frequency-dependence of perpendicular diffusivity (λ() ...
Demyelinating diseases, such as multiple sclerosis and leukodystrophy, are characterized by damage to the protective myelin sheath that surrounds the axons of neurons. This demyelination can be caused by an autoimmune response or impaired myelin production by oligodendrocytes.. A new report in JCI Insight from Arjun Saha and colleagues at Duke University demonstrates that a cell therapy product called DUOC-01 can accelerate remyelination of axons in mice treated with a demyelinating chemical agent. DUOC-01 cells, which are derived from banked umbilical cord blood, were transplanted into mice following toxic demyelination. DUOC-01 treatment resulted in faster remyelination and promoted the differentiation of oligodendrocyte progenitor cells. These results suggest that a cord blood-derived cell product can promote neuronal repair and remyelination. Future clinical studies will be needed to determine if DUOC-01 cell therapy benefits patients with demyelinating diseases.. ...
Both diets decreased disease severity compared to the control group but the Ketogenic Diet had more modest effects and did not reverse EAE progression in mice. The FMD mice group had clinical reductions to disease symptoms including higher blood levels of corticosterone, improvements in cytokines and T- Cells and a.. May 26, 2016. Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet.. A ketogenic diet. this is the diet for you. Instead, the idea is to rotate when and what you eat in three different phases to put your metabolism into overdrive. The FMD focuses on eating real food and cutting out fad diet nonsense like.. 5 day water fast results tracked via blood ketones, blood glucose and weight. Step by step walk through and experiences of several ...
Individual Test Kits (Copper) A yellow color is formed when copper reacts with diethyldithiocarbamate (DDC). A blue color is formed when copper reacts with cuprizone. ...
B,C) Analysis indicates the total distance was unchanged between cuprizone-exposed mice with or without clemastine treatment (B), but the distance in the central field decreased upon 6-week exposure to cuprizone, while clemastine gradually rescued the behavioral change (C). *P ...
There is much evidence to support the goal of remyelination as a means to prevent axon degeneration and slow deficit progression in neurologic disease [14]. In the year 2000, we reported the identification of a natural human IgM that promoted robust spinal cord remyelination in both the TMEV-IDD and lysolecithin-induced demyelination models [15, 16]. A recombinant form of this human IgM, termed rHIgM22, was expressed in a F3B6 cell line with the assembled IgM containing a mouse J chain [17]. rHIgM22 binds to myelin and the surface of oligodendrocytes (OL) and in pre-clinical studies is effective in vivo at very low doses. A single 0.025 mg/kg intraperitoneal injection of rHIgM22 given to TMEV-IDD mice with demyelination promoted significant remyelination 5 weeks later [18] and increased brainstem NAA concentrations [13], indicating a preservation of axon health [19]. In a recently concluded dose escalation clinical trial in humans with MS, rHIgM22 was tested at doses ranging from 0.025 up to 2 ...
Valery, Patricia C., Lucas, Robyn M., Williams, David B., Pender, Michael P., Chapman, Caron, Coulthard, Alan, Dear, Keith, Dwyer, Terence, Kilpatrick, Trevor. J., McMichael, Anthony J., van, der Mei, Ingrid, Taylor, Bruce and Ponsonby, Anne-Louise (2013). Occupational Exposure and Risk of Central Nervous System Demyelination. American Journal of Epidemiology,177(9):954-961. ...
Neuroprotective approaches for central nervous system regeneration have not been successful in clinical practice so far and compounds that enhance remyelination are still not available for patients with multiple sclerosis. The objective of this study was to determine potential regenerative effects of the substance cytidine-5-diphospho (CDP)-choline in two different mouse animal models of multiple sclerosis. The effects of exogenously applied CDP-choline were tested in mouse myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. In addition, the cuprizone-induced mouse model of de- and remyelination was used to specifically test the hypothesis that CDP-choline directly increases remyelination. We found that CDP-choline ameliorated the disease course of experimental autoimmune encephalomyelitis and exerted beneficial effects on myelin, oligodendrocytes and axons. After cuprizone-induced demyelination, CDP-choline effectively enhanced myelin regeneration and ...
The pathogenesis of murine hepatitis virus, strain JHM, was studied in 6- and 12-week-old C57iBL mice. There was 100% mortality in the 6-week-old mice after intracerebral inoculation. The lesions were characterized by necrotizing encephalomyelitis, without demyelination. Intracerebral inoculation of 12-week-old animals, however, resulted in no morbidity or mortality. The 12-week-old animals showed transient virus replication in the brain, spinal cord, and liver, which was cleared by day 14. Histologic examination showed evidence of ongoing demyelination, concomitant remyelination, and hydrocephalus ex vacuo. Although viral antigen was demonstrated by immunofluorescence in the central nervous system of these animals, no infectious virus was recovered, and immunosuppression regimens did not potentiate the disease.. ...
Read about Endece receiving a n additional U.S. patent covering NDC-1308 therapy, seen in early studies to have potential to induce remyelination in MS.
Although our knowledge about the formation of oligodendrocytes and their progenitors has grown enormously during the past two decades, the formulation of specif...
Multiple Sclerosis (MS) is an inflammatory disease which causes areas of demyelination in the Central Nervous System (CNS) and affects only humans. Current therapies for MS are focused on anti-inflammatory treatment, which reduce the occurrence and clinical relapses of the disease. However, progressive disability of the disease is related to axonal degeneration. After demyelination, remyelination occurs, which helps repair the demyelinated lesions and protects axons from degeneration. However, this endogenous remyelination is inefficient, and currently there are no therapies available to enhance remyelination. The aim of this thesis was to first characterize a fast and reliable model to study CNS remyelination in vitro, and second to investigate the role of semaphorin 3a (Sema3A) and semaphorin 3f (Sema3F) signaling in CNS remyelination. Various in vivo models have been developed to investigate the pathology of multiple sclerosis, and can be used to test remyelination therapies. However, in vivo ...
However, French Secretary of State for Health Dr Bernard Kouchner took the decision to ban the jab in light of evidence that the vaccine could cause multiple sclerosis or other forms of central nervous system demyelination. Studies in both France and Britain have shown that, in school aged children, the risk of demyelinating reactions in the central nervous system increases during the two months after vaccination (BMJ, 1998; 317: 1034 ...
SUPERVISORS: OLE DIDRIK LÆRUM, ØYSTEIN BRUSERUD 2000 DR.MED. PEER KÅRE LILLENG. TUMOUR CELLS IN THE AXILLARY NODES IN PATIENTS WITH BREAST CANCER. SUPERVISORS: FLORA HARTVEIT, BJØRN MÆHLE.. 1999 DR.MED. HANS KRISTIAN HAUGLAND. MODULATION OF INVASIVE BEHAVIOR IN CULTURED HUMAN GLIOMA CELLS. SUPERVISOR: OLE DIDRIK LÆRUM. 1998 DR.MED. LARS BØ. MULTIPLE SCLEROSIS. IMMUNOPATHOLOGICAL STUDIES OF INFLAMMATORY CENTRAL NERVOUS SYSTEM DEMYELINATION. SUPERVISOR: SVERRE MØRK. 1999 DR.MED. LARS FJELLBIRKELAND. THREE-DIMENSIONAL CULTURE OF HUMAN BRONCHIAL MUCOSA AND LUNG CANCER TISSUE. SUPERVISORS: OLE DIDRIK LÆRUM, ROLF BJERKVIG. 1998 DR.MED. JOHANNA OLWEUS. EARLY EVENTS IN HUMAN MYELOPOIESIS. SUPERVISORS: OLE DIDRIK LÆRUM, FRIDTJOF LUND-JOHANSEN. 1998 DR.MED. SVEIN JACOB TJOFLAAT NYGAARD. DYNAMIC DETERMINATION AND MODULATION OF GLIOMA CELL INVASION IN VITRO. SUPERVISORS: OLE DIDRIK LÆRUM, OLE BJØRN TYSNES. 1998 DR.MED. KARIN COLLETT. OPERABLE BREAST CANCER. SUPERVISORS: BJØRN MÆHLE, ROLV ...
Central nervous system (CNS) myelination is important for proper nervous system function in vertebrates. In demyelinating diseases such as multiple sclerosis, autoimmune-mediated myelin destruction results in neurological impairment; and although remyelination does occur spontaneously, it is poorly understood and insufficient in humans. Zebrafish (Danio rerio) are known to harbour tremendous regenerative capacity of various CNS tissues; however, there is presently only little knowledge of their myelin repair efficiency. An experimental model of myelin injury in zebrafish would permit study of the mechanisms involved in successful remyelination and could potentially guide the development of novel therapeutic agents for mammalian remyelination. This doctoral thesis describes the characterisation of the novel myelin protein Claudin k in zebrafish, demonstrates the establishment of adult zebrafish as an experimental model for CNS de- and remyelination and explores some mechanisms underlying myelin ...
Magnetization transfer imaging represents an attempt to develop contrast in MR imaging on the basis of submolecular exchange processes that may occur in biological tissue (21). This technique has some clinical and research applications in the study of different CNS disorders (22), because it affords a potential window into the macromolecular environment that is not directly visible using conventional techniques (21). Therefore, it enables the assessment of "invisible" disease in the so-called normal-appearing white matter (23-25), and, with the application of MTR, it provides a means to quantify disease burden (26).. Experimental and human studies support the hypothesis that demyelination and axonal loss are the main contributors to the MTR decrease observed in association with several pathologic conditions, such as experimental autoimmune encephalomyelitis (12), toxic demyelination (27), progressive multifocal leukoencephalopathy (28), human immunodeficiency virus encephalitis (28), and ...
Dr Jessica Fletcher, funded by an MS Research Australia Postdoctoral Fellowship, with the support of the Trish MS Research Foundation, has been working with Dr Simon Murray and Dr Junhua Xiao at The University of Melbourne, investigating novel molecular targets for promoting remyelination in the brain. Myelin coats the nerve cells in the brain and spinal cord. In MS there is damage to the myelin, and in the early stages of the disease there is some ability to repair the myelin, a process known as remyelination. Over time the bodys ability to remyelinate becomes impaired, leading to incomplete repair and contributing to the progression of MS symptoms. It is crucial to identify potential new treatment targets that can promote myelin repair, prevent nerve damage and halt MS disease progression.. Dr Fletcher has been working on a nerve growth factor, known as brain-derived neurotrophic factor (BDNF), which has been found to promote myelination by activating different receptors, or docking stations, ...
Read about an MS study showing the protein EphrinB3 blocks remyelination by inhibiting oligodendrocyte formation, and suggesting it as a treatment target.
... can be extensive in multiple sclerosis despite a long disease course 21 April 2007 Patani R, Balaratnam M, Vora A, Reynolds R. Department of Cellular and Molecular Neuroscience, UK MS Tissue Bank, Division of Neuroscience, Imperial College London, Charing ...
Research on myelination offers centered on identifying molecules capable of inducing oligodendrocyte (OL) differentiation in an effort to develop strategies that promote functional myelin regeneration in demyelinating disorders. of and gene manifestation, mediated from the connection of SMAD3/4 with Sp1 and FoxO1 transcription factors. Our study is the 1st to demonstrate an autonomous and important part of TGF signaling in OL development and CNS myelination, and may provide new avenues in the treatment of demyelinating diseases. studies have shown that O-2A progenitor cells express TGF1 and that TGF signaling activation exerts an anti-mitogenic effect countering PDGFR signaling, in turn promoting cell cycle arrest (McKinnon et al., 1993). Moreover, Activin-A, a member of the TGF superfamily, has been proposed as one of the cytokines secreted by microglial cells that plays a role in OL regeneration and remyelination (Miron et al., 2013). These scholarly research claim that TGF signaling could be ...
TY - PAT. T1 - Treatment of Demyelinating Disorders with Soluble Lymphotoxin-Beta-Receptor. AU - Browning,Jeffrey L.. AU - Ting,Jenny P-Y. N1 - Status: published applicationnumber: 12/446,041 usclass: 514/19.2 ; 514/1.1; 530/351 applicationnumber: 12/446,041. PY - 1800. Y1 - 1800. N2 - Methods of treating a demyelinating disorder using inhibitors of the lymphotoxin pathway.. AB - Methods of treating a demyelinating disorder using inhibitors of the lymphotoxin pathway.. M3 - Patent. M1 - 8067375. ER - ...
Remyelination is the process of propagating oligodendrocyte precursor cells to form oligodendrocytes to create new myelin sheaths on demyelinated axons in the CNS. This is a process naturally regulated in the body and tends to be very efficient in a healthy CNS. The process creates a thinner myelin sheath than normal, but it helps to protect the axon from further damage, from overall degeneration, and proves to increase conductance once again. Demyelinating diseases, such as Multiple Sclerosis, have been of utmost interest within the last couple of decades. Recent research is uncovering some of the many unknown pathways involved with remyelination in hopes of battling demyelinating diseases like MS which can ultimately cripple a person. While no treatment exists yet in preventing remyelination failure in the chronic stages of these diseases, future research may yet prove to unlock key pathways that can be targeted. Remyelination is activated and regulated by a variety of factors surrounding ...
We set up the Cambridge Centre for Myelin Repair in 2005, with the aim of developing treatments that promote myelin repair for people with MS.. Since it opened the Cambridge Centre has created a world-class research environment involving researchers from all around the UK - most notably at our Edinburgh Centre for MS Research.. Scientists at both centres have worked together to show that a molecule called RXR-gamma could encourage the brains own stem cells to repair myelin in animal models of MS. Researchers will now test the benefits of a drug that targets RXR-gamma, called bexarotene, in a phase 2 clinical trial.. We announced four more years of funding for the Cambridge Centre in 2016. Researchers will continue to investigate the fundamental mechanisms behind myelin repair, with the hope of developing new treatments.. They will focus on understanding more about the cells capable of repairing myelin, and the impact ageing and lifestyle factors (such as diet and exercise) can have on these ...
In the present study, we show that hypomyelination in the MLIV mouse brain is associated with decreased expression of both precursor and mature oligodendrocyte markers, as well as a decrease in the number of postmitotic oligodendrocytes. Our observation of delayed myelin deposition during early postnatal brain development highlights the developmental character of brain pathology in MLIV. Interestingly, our data also indicate that the fate of developing oligodendrocytes is affected differently in the white (corpus callosum) versus gray (neocortex) matter of the brain as indicated by changes in CC+ cell counts (Fig. 4) or PLP and MBP staining intensities in these brain regions. This suggests that the tissue microenvironment and factors released by neighboring cells can contribute to the ability of Mcoln1−/− oligodendrocytes to develop, survive and/or produce myelin. Despite these region-specific changes within the brain, our data demonstrate that TRPML1 is an important regulator of ...
Demyelinating Disorders of the Central Nervous System in Childhood von Chabas/Waubant Chabas/Waubant und Buchbewertungen gibt es auf ReadRate.com. Bücher können hier direkt online erworben werden.
Dr. Fabrizio Salvi- Head neurologist at the University of Bologna spoke of his clinical observations as a neurologist working with the CCSVI paradigm for three years. He told us that in 500 MS patients he has tested now, 100% have CCSVI. He stated the doppler is a wonderful tool of diagnosis and their needs to be training in the technique. He has a hypothesis as to why there are different varieties of screening in high risk subjects- because prognosis is related to the type of malformation. He wants to answer the question if the Liberation procedure is a disease modifying treatment in MS. He will give proof tomorrow that there is plasticity and remyelination in the CNS and the Liberation procedure have proven to activate remyelination in the CNS as shown by MRI ...
Graham S.T. Smith is the author of this article in the Journal of Visualized Experiments: Monitoring Cleaved Caspase-3 Activity and Apoptosis of Immortalized Oligodendroglial Cells using Live-cell Imaging and Cleaveable Fluorogenic-dye Substrates Following Potassium-induced Membrane Depolarization
Video articles in JoVE about myelin basic proteins include Monitoring Cleaved Caspase-3 Activity and Apoptosis of Immortalized Oligodendroglial Cells using Live-cell Imaging and Cleaveable Fluorogenic-dye Substrates Following Potassium-induced Membrane Depolarization.
Current treatment modalities for the neurodegenerative disease multiple sclerosis (MS) use disease-modifying immunosuppressive compounds but do not promote repair. Although several potential targets that may induce myelin production have been identified, there has yet to be an approved therapy that promotes remyelination in the damaged central nervous system (CNS). Remyelination of damaged axons requires the generation of new oligodendrocytes from oligodendrocyte progenitor cells (OPCs). Although OPCs are detected in MS lesions, repair of myelin is limited, contributing to progressive clinical deterioration. In the CNS, the chemokine CXCL12 promotes remyelination via CXCR4 activation on OPCs, resulting in their differentiation into myelinating oligodendrocytes. Although the CXCL12 scavenging receptor CXCR7/ACKR3 (CXCR7) is also expressed by OPCs, its role in myelin repair in the adult CNS is unknown. ...
... is a chapter in the book, Neurology, containing the following 2 pages: Multiple Sclerosis, Guillain Barre Syndrome.
MS Focus: the Multiple Sclerosis Foundation provides grants and services to meet the critical needs of people with MS and their families.
Myelin is the insulation sheath around nerve fibres. If this protective layer is injured, the affected nerves are no longer functional. The adult brain contains …
Demyelination of CNS axons occurs in a number of pathological conditions, including multiple sclerosis and contusion-type spinal cord injury. The demyelination can be repaired by remyelination in both humans and rodents, and even within the CNS remyelination can be achieved by endogenous and/or exogenous Schwann cells, the myelinating cells of the PNS. Remyelinated axons can often conduct impulses securely, but the organization of ion channels at long-term remyelinated nodes is not known. In the present study, the expression of voltage-gated sodium (Nav) and potassium (Kv) channels along central axons remyelinated by endogenous Schwann cells has been studied in lesions induced more than 1 year previously by the intraspinal injection of ethidium bromide (EB). The expression of the channels at long-term nodes formed by Schwann cell remyelination has been compared with that present in nascent nodes formed in the adult at 18 and 23 days post-EB injection. Immunohistochemical studies revealed that ...
Loss of oligodendrocytes in multiple sclerosis (MS) leads to demyelination and axonal dysfunction and transection. Myelin repair, or remyelination, not only restores proper axonal conduction, but also protects axons from degeneration. Oligodendrocytes are myelin-producing cells and are generated from oligodendrocyte progenitor cells (OPCs). Although spontaneous production of oligodendrocytes and consequent remyelination do occur in early phases of MS, the efficiency decreases over time as the disease progresses. Therapeutic interventions to stimulate oligodendrocyte production and remyelination efficiency are likely to reduce disease progression and neurological disability ...
Early in 2016 Dr David Gonsalvez was awarded a prestigious Betty Cuthbert Postdoctoral Fellowship co-funded by National Health and Medical Research Council / MS Research Australia, with MS Research Australias contribution provided with full funding support from the Trish MS Research Foundation. MS results from the damage and loss of myelin, the conductive layer present around nerve fibres in the brain and spinal cord. This makes the nerve fibres unable to transmit their electrical signals, but also leaves the nerves very vulnerable to permanent damage. Myelin can be repaired, but this process is often incomplete and the failure of remyelination is thought to contribute to the development of the secondary progressive form of MS. At the moment there are no treatment options available that promote the repair of myelin to restore lost function and prevent further disability in people with MS. It is known the myelin repair is inhibited by some of the chemicals and physical features associated with ...
An innovative funding scheme generates ground-breaking progress in understanding the genetic changes in MS as well as myelin repair.
Myelin is the sheathing of nerves, essential to their function. Excessive loss produces disabling and ultimately fatal conditions such as multiple sclerosis, but we all lose myelin integrity to some degree as a consequence of the damage and dysfunction of degenerative aging. This most likely contributes to cognitive decline and other age-related issues. A number of different approaches have been i...
New cases of central nervous system demyelination and exacerbations of pre-existing disease have been reported in patients with rheumatoid arthritis following exposure to TNF inhibitors. However, as in the case of lymphoma, any causal relationship remains controversial and unproven. In fact, TNF-a has been implicated in the pathogenesis of multiple sclerosis, and because of this there have been studies of TNF inhibitors in this disease. In a Phase I open-label study, two patients with rapidly progressing multiple sclerosis refractory to high-dose intravenous corticosteroids were treated with intravenous infliximab. Both patients were found to have an increase in the number of gadolinium-enhancing lesions on MRI, together with increases in CSF leucocyte counts after each infusion. However, these changes were not accompanied by neurological deterioration (van Oosten et al. 1996). In a Phase II multicentre study, 168 patients with relapsing-remitting and secondary progressive multiple sclerosis ...
Multiple sclerosis involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system. Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells are stem cells in the central nervous system and the principal source of myelinating oligodendrocytes. These cells are abundant in demyelinated regions of patients with multiple sclerosis, yet fail to differentiate, thereby representing a cellular target for pharmacological intervention. To discover therapeutic compounds for enhancing myelination from endogenous oligodendrocyte progenitor cells, we screened a library of bioactive small molecules on mouse pluripotent epiblast stem-cell-derived oligodendrocyte progenitor cells. Here we show seven drugs function at nanomolar doses selectively to enhance the generation of mature oligodendrocytes ...
Free Essay: Multiple Sclerosis (MS) is an autoimmune demyelinating disorder it is characterized by inflammation and destruction of CNS myelin. It affects...
The present study identifies cAMP‐Erk1/2/p38Mapk‐Creb1 signalling as a functionally important intracellular signalling cascade for CNS remyelination that is regulated at the earliest stages of OPC differentiation. These data complement previous studies demonstrating a role for Erk2 and p38Mapk (Chew et al, 2010) as positive regulators of oligodendrocyte differentiation in vitro and during developmental myelination. Loss of ERK2 attenuates OPC differentiation and leads to a delay but not a complete arrest in the appearance of differentiated oligodendrocytes in vivo (Fyffe‐Maricich et al, 2011). Similarly, p38Mapk inhibition decreases OPC differentiation and Mbp expression without effecting either proliferation or survival (Chew et al, 2010). Reporter assay studies have demonstrated that p38MAPK activity up‐regulates the activity and/or expression of transcription factors that can bind the 2 kb mouse MBP promoter. However, p38MAPK can also antagonize ERK, JNK, c‐Jun phosphorylation. We ...
The polyanion-binding cell surface receptor TREM2 is expressed on myeloid cell populations, including microglia of the CNS. Individuals with inactivating mutations in TREM2 or TYROBP, which encodes the TREM2 adapter DAP12, develop Nasu-Hakola disease, a rare, lethal dementia that manifests in early adulthood and is characterized by demyelinating lesions. The link between loss of TREM2 function and dysfunctional myelination is not clear. Pietro Poliani, Yaming Wang, and colleagues at the University of Brescia School of Medicine used murine models to investigate a possible role for microglial TREM2 in myelin repair following injury. An age-dependent expansion of microglia was absent in the brains of mice lacking TREM2, and the microglia that were present were notably smaller and dystrophic. In a chronic toxin model of demyelination, loss of TREM2 severely impaired remyelination and removal of myelin debris during prolonged toxin exposure. Further, Trem2 deletion altered demyelination- and ...
The polyanion-binding cell surface receptor TREM2 is expressed on myeloid cell populations, including microglia of the CNS. Individuals with inactivating mutations in TREM2 or TYROBP, which encodes the TREM2 adapter DAP12, develop Nasu-Hakola disease, a rare, lethal dementia that manifests in early adulthood and is characterized by demyelinating lesions. The link between loss of TREM2 function and dysfunctional myelination is not clear. Pietro Poliani, Yaming Wang, and colleagues at the University of Brescia School of Medicine used murine models to investigate a possible role for microglial TREM2 in myelin repair following injury. An age-dependent expansion of microglia was absent in the brains of mice lacking TREM2, and the microglia that were present were notably smaller and dystrophic. In a chronic toxin model of demyelination, loss of TREM2 severely impaired remyelination and removal of myelin debris during prolonged toxin exposure. Further, Trem2 deletion altered demyelination- and ...
Multiple Sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system (CNS). The etiology of MS remains unclear, but the disease deve...
Research proven mouse monoclonal Olig1,2,3 Antibody. Excellent marker for oligodendrocyte progenitor cells. Referenced in customer publications.
Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of Olig2. Also described herein are methods of using such Olig2 inhibitors, alone and in combination with other compounds, for treating cancer and other diseases. In particular the Olig2 inhibitors may be used to treat glioblastoma.
Central nervous system idiopathic inflammatory demyelinating disorders are a heterogenous group of diseases that share inflammation and demyelination as key features. Although the exact pathophysiology remains to be fully unveiled, these conditions are challenging to clinicians who seek specific therapeutic options for their patients. For two of these conditions, multiple sclerosis and neuromyelitis optica, there are now several possible therapies in an ever-evolving field. This review will touch on the various idiopathic inflammatory demyelinating disorders and discuss the various treatment options currently available.
Central pontine myelinolysis (CPM) is an acute demyelination within the central basis pontis. Though exact mechanism is not known it is seen commonly with rapid correction of hyponatremia and also with pontine ischemia or infarction, demyelinating di
A novel method has been developed for the preparation of nearly pure separate cultures of astrocytes and oligodendrocytes. The method is based on (a) the absence of viable neurons in cultures prepared from postnatal rat cerebra, (b) the stratification of astrocytes and oligodendrocytes in culture, and (c) the selective detachment of the overlying oligodendrocytes when exposed to sheer forces generated by shaking the cultures on an orbital shaker for 15--18 h at 37 degrees C. Preparations appear greater than 98% pure and contain approximately 1-2 x 10(7) viable cells (20--40 mg of cell protein). Three methods were used to characterize these two culture t ypes. First, electron microscopic examination was used to identify the cells in each preparation (mixed and separated cultures of astrocytes and oligodendrocytes) and to assess the purity of each preparation. Second, two oligodendroglial cell markers, 2,3-cyclic nucleotide 3-phosphohydrolase (EC 3.1.4.37) and glycerol phosphate dehydrogenase ...
The journal focuses on neuroimmunology and neuroinflammation, and the coverage extends to other basic and clinical studies related to neuroscience including molecular biology, psychology, pathology, physiology, endocrinology, pharmacology, oncology, etc.
Multiple sclerosis, which is the most common cause of chronic neurological disability in young adults, is an inflammatory, demyelinating, and neurodegenerative disease of the CNS, which leads to the formation of multiple foci of demyelinated lesions in the white matter. The diagnosis is based currently on magnetic resonance image and evidence of dissemination in time and space. However, this could be facilitated if biomarkers were available to rule out other disorders with similar symptoms as well as to avoid cerebrospinal fluid analysis, which requires an invasive collection. Additionally, the molecular mechanisms of the disease are not completely elucidated, especially those related to the neurodegenerative aspects of the disease. The identification of biomarker candidates and molecular mechanisms of multiple sclerosis may be approached by proteomics. In the last 10 years, proteomic techniques have been applied in different biological samples (CNS tissue, cerebrospinal fluid, and blood) from ...
Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system commonly affecting young adults. Pathologically, there are patches of inflammation (plaques) with demyelination of axons and oligodendrocyte loss. There is a global latitude gradient in MS prevalence, and incidence of MS is increasing (particularly in females). These changes suggest a major role for environmental factors in causation of disease. We have reviewed the evidence and potential mechanisms of action for three exposures: vitamin D, Epstein Barr virus and cigarette smoking. Recent advances supporting gene-environment interactions are reviewed. Further research is needed to establish mechanisms of causality in humans and to explore preventative strategies.
Our research group is interested in the molecular mechanisms defining the epigenetic state of stem/progenitor cells. We are particularly focused on how interplay between transcription factors, non-coding RNAs and chromatin modifying enzymes contributes to the transition between epigenetic states in oligodendrocyte precursor cells, with the aim to design epigenetic based-therapies to induce regeneration (remyelination) in demyelinating diseases, such as multiple sclerosis.
MS and RA patient advocate, Lisa Emrich, shares news and information about living with multiple sclerosis and rheumatoid arthritis while working as a musician in Washington, DC.
Well my neuro called after my follow up MRI from last week. (On 3T machine this time) Demyelinating lesions were found on my brain this time and he diagnosed me with MS. Background info on me: prev...
TY - JOUR. T1 - Allelic variation in the Tyk2 and EGF genes as potential genetic determinants of CNS repair. AU - Bieber, Allan J.. AU - Suwansrinon, Kanitta. AU - Kerkvliet, Jason. AU - Zhang, Weidong. AU - Pease, Larry R.. AU - Rodriguez, Moses. PY - 2010/2/15. Y1 - 2010/2/15. N2 - The potential for endogenous remyelination and axonal protection can be an important factor in determining disease outcome in demyelinating diseases like multiple sclerosis. In many multiple sclerosis (MS) patients CNS repair fails or is incomplete whereas in others the disease is accompanied by extensive repair of demyelinated lesions.We have described significant differences in the ability of two strains ofmice to repair CNS damage following Theilers virusinduced demyelination: FVB/NJ (FVB) mice repair damaged myelin spontaneously and completely,whereas B10.D1-H2q/SgJ (B10.Q)mice are deficient in the repair process. A QTL analysis was performed to identify genetic loci that differentially regulate CNS repair ...
The most common neurological deficits in children after surgery for congenital heart disease are fine and gross motor deficits. Recent magnetic resonance imaging studies have demonstrated a significant number of newly developed white matter (WM) lesions in infants after surgery. The present study describes region-specific WM development in the juvenile porcine brain, which is similar in developmental stage to the human newborn. Acute and long-term cellular responses to cardiopulmonary bypass in oligodendrocyte lineages and neuron-axonal elements, which are the most prominent cell populations in WM, have been observed. A uniquely susceptible cellular target of cardiopulmonary bypass-induced WM injury in the oligodendrocyte lineage, as well as maturation-dependent vulnerability of developing WM, was found. Oligodendrocyte progenitor cells, which mediate WM recovery function, are highly resistant to cardiopulmonary bypass-induced injury. Interestingly, oligodendrocyte progenitor cell number ...
A recent study analyzed the role of purinergic receptor P2X4 in microglia/macrophages during autoimmune inflammation, finding that P2X4 receptors modulate microglia/macrophage inflammatory responses and identify allosteric modulator ivermectin (IVM) as a potential candidate to promote the repair of myelin damage.
Parkinsons Disease: Brain: Corpus Callosum, 1 mg. Tissue total protein is prepared from whole tissue homogenates and presents a consistent pattern on SDS-PAGE analysis.
(mid-sagittal brain fibers that connect the two hemispheres through the corpus callosum, photographed by Thomas Schultz--2006) In my last post, which you can read here, I noted that it is important for me to take some quiet moments to listen to what my emotional body is telling me. If Im able to do that I can…
Silverstroff, L.; Batucci, S.; Pasquini, J.; Franco, P. (2012). "Cuprizone-induced demyelination in the rat cerebral cortex and ... "The cyclooxygenase-2 pathway via the pge₂ ep2 receptor contributes to oligodendrocytes apoptosis in cuprizone-induced ...
"Cerebroside synthesis as a measure of the rate of remyelination following cuprizone-induced demyelination in brain". Journal of ...
... the resolution of status spongiosus and remyelination in cuprizone intoxication in mice". J. Neurocytol. 1 (4): 413-26. doi: ...
... lacking mice also exhibit a different regulation of this protein after oligodendrocyte damage induced by the chemical cuprizone ...
Elevated expression of GPR84 was also observed during the demyelination phase of the reversible Cuprizone-Induced Demyelinating ...
In acute or chronic demyelinated lesions created in the rodent CNS by chemical agents such as lysolecithin or cuprizone, ...
... cuprizone MeSH D02.455.426.392.368.367.204 --- cyclamates MeSH D02.455.426.392.368.367.218 --- cyclohexanecarboxylic acids MeSH ...
Transfer of Myelin-Reactive Th17 Cells Impairs Endogenous Remyelination in the Central Nervous System of Cuprizone-Fed Mice ... Astrocyte-Derived BDNF Supports Myelin Protein Synthesis after Cuprizone-Induced Demyelination Clifton G. Fulmer, Melissa W. ...
After cuprizone, the HA+ non-GFAP+ cells are greatly reduced. When cuprizone-treated mice are injected with ACPD, there is an ... Cuprizone treatment. Demyelination was initiated by feeding 8-week-old wild-type male mice or HA male mice 0.2% cuprizone ( ... To evaluate the effects of ACPD in the cuprizone model, wild-type mice treated with cuprizone received a single stereotaxic ... Wild-type mice were fed control or cuprizone-laden food for 4 weeks. NF-L+ axons fail to colocalize with (a) mGluR1, or (b) ...
Using transgenic mice to fate map and to selectively kill SVZ-derived eNPCs in the cuprizone demyelination model, we observed ... First, we fate mapped SVZ-eNPCs in cuprizone-induced demyelination and found that SVZ endogenous neural stem/precursor cells ... When we ablated SVZ-derived eNPCs during cuprizone-induced demyelination in female mice, the animals displayed reduced numbers ... Neural Stem Cells of the Subventricular Zone Contribute to Neuroprotection of the Corpus Callosum after Cuprizone-Induced ...
... the effects of cuprizone on the functions of the peripheral nervous system, as well as differential effects it may exert on ... Cuprizone induces massive demyelination in the CNS; however, ... Cuprizone led to a reduction in the NCV, CMAP amplitude and ... Cuprizone induces massive demyelination in the CNS; however, the effects of cuprizone on the functions of the peripheral ... S. Love, "Cuprizone neurotoxicity in the rat: Morphologic observations," J. Neurol. Sci., 84, Nos. 2/3, 223-237 (1988).CrossRef ...
C57Bl/6 mice were fed chow containing 0.7% cuprizone for 1 week, followed by 3 weeks of a 0.2% cuprizone diet. Linagliptin (10 ... Linagliptin attenuated cuprizone-induced oxidative stress by decreasing brain thiobarbituric acid reactive substances along ... Home » Topics » Spinal Cord Disorders » Research » Neuroprotective effect of linagliptin against cuprizone-induced ... This study investigated the possible neuroprotective effect of linagliptin against cuprizone-induced demyelination in mice and ...
We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice. ... Methods: Adult male C57BL/6 mice (n = 40) were fed a regular diet or a diet containing cuprizone (0.2% w/w) for 6 six weeks. ... We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice. ... Cuprizone could decrease myelin-binding protein mRNAs expression in corpus callosum, which was significantly recovered after BM ...
A common model of acute demyelination oral administration of copper-depleting cuprizone (CPZ) holds promise for defining ... Chronic white matter atrophy after acute cuprizone exposure may be due to transmissible misfolded proteins ...
To analyze its role in the demyelinating situation, we employed cuprizone (CPZ)-induced demyelination model in mice, which is ... To analyze its role in the demyelinating situation, we employed cuprizone (CPZ)-induced demyelination model in mice, which is ... Cuprizone Administration. To induce demyelination in 10-week-old ICR male mice, they were administered a diet containing 0.4% ... Cuprizone (CPZ)-induced experimental demyelination is a suitable rodent model to study the mechanisms leading to demyelination ...
Animals were fed with 0.2% w/w cuprizone added to ground breeder chow ad libitum for six weeks. At day 0 after cuprizone ... Index: IMEMR (Eastern Mediterranean) Main subject: Adipose Tissue / Cuprizone / Mesenchymal Stem Cell Transplantation / Mice ... Promotion of remyelination by adipose mesenchymal stem cell transplantation in a cuprizone model of multiple sclerosis ... Promotion of remyelination by adipose mesenchymal stem cell transplantation in a cuprizone ...
Four groups of rats were treated with normal saline, cuprizone, M. oleifera and a combination of M. oleifera and cuprizone, for ... Cuprizone is a neurotoxin with copper-chelating ability used in animal model of multiple sclerosis in which oxidative stress ... Animals , Brain , Catalase , Cuprizone , Hippocampus , Memory , Memory, Short-Term , Models, Animal , Moringa oleifera , ... Cuprizone significantly induced oxidative and nitrosative stress coupled with memory decline and cortico-hippocampal neuronal ...
... as compared to cuprizone-treated mice with control MSC grafts and/or cuprizone-treated mice without MSC injection. In the first ... Next, CNS inflammation and demyelination was induced by means of a cuprizone-supplemented diet. The influence of IL13-MSC ... limits cuprizone-induced microgliosis, oligodendrocyte death and demyelination. Furthermore, we here demonstrate that injection ... and to interfere with oligodendrocyte death and demyelinating events in the cuprizone mouse model. ...
... without cuprizone)" and at "3 and 5 weeks cuprizone feeding" in the new Figure 8. Unfortunately, we could not expand the data ... Alleviation of cuprizone-induced demyelination in SIRPα cKO mice.. (A) Control (SIRPα-flox:- (Ctrl)) or SIRPα cKO (SIRPα-flox: ... Cuprizone model of demyelination. Request a detailed protocol Control (SIRPα-flox:-) or SIRPα cKO (SIRPα-flox:Cx3cr1CreERT2) ... Alleviation of cuprizone-induced demyelination in the brain white matter of microglia-specific SIRPα-deficient mice. Although ...
Demyelination by cuprizone diet. Mice were placed on a diet of 0.2% (wt/wt) cuprizone mixed into chow pellets. Mice were ... MH helped with tamoxifen injection and cuprizone feeding. HF, MY, and HM provided autopsied samples. M Konishi and NI ... Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite an intact blood-brain barrier. J Neuroimmunol ... Kondo A, Nakano T, Suzuki K. Blood-brain barrier permeability to horseradish peroxidase in twitcher and cuprizone-intoxicated ...
Cuprizone induced demyelination. Chow containing 0.2% cuprizone (Harlan Teklad) was fed to C57Bl mice (N = 7) ad libitum for 3 ... Cuprizone demyelination does not cause CD45 activation in the SVZ. A, B) CD45 expression is minimal in control corpus callosum ... Cuprizone induced demyelination does not induce CD45 activation in the SVZ. We next asked whether the massive CD45 cell ... Cuprizone, a copper chelating agent induces demyelination in a variety of CNS regions including immediately above the SVZ, in ...
The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. ... Home » Papers » The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system ...
... and benztropine is required in the cuprizone model to improve remyelination. Our data further support tuftsins beneficial ... and benztropine is required in the cuprizone model to improve remyelination. Our data further support tuftsins beneficial ... in both EAE and in the cuprizone model of demyelination. We show that combining these two agents to promote anti-inflammatory ... in both EAE and in the cuprizone model of demyelination. We show that combining these two agents to promote anti-inflammatory ...
PET imaging of demyelination and remyelination in the cuprizone mouse model for multiple sclerosis: a comparison between [11C] ... Transplantation into adult shiverer mice resulted in phenotypic rescue; it also ameliorated demyelination in a cuprizone mouse ... 2. Focus on benztropine; PLP-induced EAE model; T cell independent cuprizone model*. 11:03 ... with demyelination chemically induced using cuprizone) suggested that benzatropine works by enhancing myelination. However, ...
Torkildsen, Øivind Fredvik; Brunborg, Linn Anne Bjelland; Myhr, Kjell-Morten; Bø, Lars. 2008. The cuprizone model for ... Wergeland, Stig; Torkildsen, Øivind; Myhr, Kjell-Morten; Mørk, Sverre; Bø, Lars. 2012. The cuprizone model: regional ... A salmon based diet protects mice from behavioural changes in the cuprizone model for demyelination. Clinical Nutrition. 83-87 ... Fish diet prevents impaired mobility in the murine cuprizone model for multiple sclerosis. Multiple Sclerosis. S90-S91. ...
Dietary Vitamin D3 Supplements Reduce Demyelination in the Cuprizone Model  Wergeland, Stig; Torkildsen, Øivind; Myhr, Kjell- ...
In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα ... cuprizone (Cpz) diet. After 3 or 5 wks of Cpz feeding (Cpz 3 wks, Cpz 5 wks), brain samples were prepared. Other groups of mice ...
Myelin, copper, and the cuprizone model of schizophrenia. Nicole R. Herring, Christine Konradi. [Frontiers In Bioscience, ...
Resveratrol Promotes Remyelination in Cuprizone Model of Multiple Sclerosis: Biochemical and Histological Study. Mol Neurobiol ...
5), and astrocytes have been proposed to play an important role in the protective effect of laquinimod in cuprizone-induced CNS ... 2012) Reduced astrocytic NF-κB activation by laquinimod protects from cuprizone-induced demyelination. Acta Neuropathol 124(3): ... demyelination (36). Laquinimod treatment reverses cuprizone-induced astrogliosis and leads to decreased production of ...
Proteomic comparison of cuprizone and experimental autoimmune encephalomyelitis MS models in mouse and translation to human ... Proteomic comparison of cuprizone and experimental autoimmune encephalomyelitis MS models in mouse and translation to human ... Proteomic comparison of cuprizone and experimental autoimmune encephalomyelitis MS models in mouse and translation to human. ... Remyelinisering i Cuprizone- modellen Agnes Nystad, Helse Bergen HF. Prosjektperiode:2012 - 2013Deltakende helseregion:HV ...
  • This targeted anti-inflammatory agent improves physical deficits in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we sought to determine whether tuftsin is also effective in combination with benztropine, an FDA-approved drug that stimulates remyelination, in both EAE and in the cuprizone model of demyelination. (frontiersin.org)
  • The EAE (experimental autoimmune encephalomyelitis) series of MS models are widely used to test therapies targeting the inflammation component of MS, while MS models where demyelination is induced by cuprizone, lysolecithin, or ethidium bromide are increasingly being used to test therapeutic candidates. (criver.com)
  • Animals were fed with 0.2% w/w cuprizone added to ground breeder chow ad libitum for six weeks. (bvsalud.org)
  • This study aimed at evaluating the ameliorative capability of M. oleifera in cuprizone-induced behavioral and histopathological alterations in the prefrontal cortex and hippocampus of Wistar rats. (bvsalud.org)
  • Lack of cuprizone-induced demyelination in the murine spinal cord despite oligodendroglial alterations substantiates the concept of site-specific susceptibilities of the central nervous system. (tiho-hannover.de)
  • BM-MSCs (2 × 10 6 in 1 milliliter medium) were administered intraperitoneally for two consecutive weeks at the end of the forth weeks of cuprizone administration. (ac.ir)
  • Four groups of rats were treated with normal saline, cuprizone, M. oleifera and a combination of M. oleifera and cuprizone, for five weeks. (bvsalud.org)
  • Cuprizone was orally administered at a dose of 400 mg/kg/day by oral gavage for 5 weeks. (medworm.com)
  • Thus, we aimed to examine changes in the electromyographic characteristics of female and male Sprague-Dawley rats with cuprizone-induced demyelination. (springer.com)
  • Notably, electrophysiological observations reveal that cuprizone affects both female and male rats, but males are more sensitive. (springer.com)
  • Importantly, tuftsin is required to transform the inflammatory CNS environment normally present in EAE/MS into one of an anti-inflammatory nature, and benztropine is required in the cuprizone model to improve remyelination. (frontiersin.org)
  • 1991. A comparison of spongiosis induced in the brain by hexachlorophene, cuprizone and triethyl tin in the Sprague-Dawley rat. (nih.gov)
  • however, administration of M. oleifera significantly reversed the neuropathological deficits induced by cuprizone. (bvsalud.org)
  • however, the effects of cuprizone on the functions of the peripheral nervous system, as well as differential effects it may exert on males and females, have not yet been studied. (springer.com)
  • This is the first study showing gender differences for the peripheral neurotoxicity of cuprizone. (springer.com)
  • During the second course of Cuprizone, the animals showed greater resistance to the toxin and demyelination occurred slowly and was complete only after prolonged periods. (docme.ru)
  • Linagliptin treatment improved behavioural and motor abnormalities induced by cuprizone, as demonstrated by open field, rotarod and grip strength tests. (bioportfolio.com)
  • BM-derived cells are recruited in a CCR2-dependent manner into demyelinating sites of the CNS in the cuprizone model. (rupress.org)