Definitions and Summary. New-onset refractory status epilepticus (NORSE) is defined as a condition, not a specific diagnosis, with new onset of refractory status epilepticus without a clear acute or active structural, toxic or metabolic cause in a patient without active epilepsy. Status epilepticus (SE) is a condition of prolonged seizure activity or repeated seizures without full recovery in between. Status epilepticus that persists despite at least two standard anti-seizure medications is termed refractory status epilepticus (RSE). Most of the common causes of RSE can be identified within 24-72 hours of presentation.. Febrile infection-related epilepsy syndrome (FIRES) is a subcategory of NORSE that requires a prior febrile infection starting between 2 weeks and 24 hours prior to onset of refractory status epilepticus, with or without fever at onset of status epilepticus.. In up to half of the cases of NORSE, a possible or probable cause is ultimately found, most often autoimmune or ...

TY - JOUR. T1 - Origins of Temporal Lobe Epilepsy. T2 - Febrile Seizures and Febrile Status Epilepticus. AU - Patterson, Katelin P.. AU - Baram, Tallie Z.. AU - Shinnar, Shlomo. PY - 2014/1/1. Y1 - 2014/1/1. N2 - Temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) commonly arise following early-life long seizures, and especially febrile status epilepticus (FSE). However, there are major gaps in our knowledge regarding the causal relationships of FSE, TLE, HS and cognitive disturbances that hamper diagnosis, biomarker development and prevention. The critical questions include: What is the true probability of developing TLE after FSE? Are there predictive markers for those at risk? A fundamental question is whether FSE is simply a marker of individuals who are destined to develop TLE, or if FSE contributes to the risk of developing TLE. If FSE does contribute to epileptogenesis, then does this happen only in the setting of a predisposed brain? These questions are addressed within this ...

Epilepsy is a very complex disorder of the central nervous system. It is characterized by a sudden, disordered and excessive neuronal shock that causes different clinical evidences with specific related electroencephalogram (EEG). Psychogenic Non-Epileptic Seizures (PNES) can seriously complicate the diagnosis of epilepsy. The separoxysmal events have the same clinical evidences of epilepsy, such as an impairment of the self-control and a range of sensory, motor and mental manifestations, without the typical related electroencephalogram (EEG) because of the absence of an organic cause. The overwhelming majority of Psychogenic Non-Epileptic Seizures are related to psychological factors like dissociation. This is a defense mechanism used to cope stressful events or emotional conflicts. Psychological or psychiatric disorders, like Post Traumatic Stress Disorder (PTSD), are frequently associated to Psychogenic Non-Epileptic Seizures. In this article, we present a case report of epilepsy combined with

Description of disease Epilepsy or seizures - discharge . Treatment Epilepsy or seizures - discharge . Symptoms and causes Epilepsy or seizures - discharge Prophylaxis Epilepsy or seizures - discharge

TY - JOUR. T1 - Bidirectional shift of group III metabotropic glutamate receptor-mediated synaptic depression in the epileptic hippocampus. AU - Dammann, Fabian. AU - Kirschstein, Timo. AU - Guli, Xiati. AU - Müller, Steffen. AU - Porath, Katrin. AU - Rohde, Marco. AU - Tokay, Tursonjan. AU - Köhling, Rüdiger. PY - 2018/1/1. Y1 - 2018/1/1. N2 - A common function of group III metabotropic glutamate receptors (mGluRs) located at the presynaptic site of a glutamatergic synapse is synaptic depression. Here, we studied synaptic depression mediated by group III mGluR activation at Schaffer collateral-CA1 (SC-CA1) synapses and associational-commissural-CA3 (AC-CA3) synapses by recording field excitatory postsynaptic potentials in the in vitro brain slice preparation. In order to gauge the impact of synaptic depression in chronically epileptic tissue, we compared rats after pilocarpine-induced status epilepticus (post-SE) with control animals. We observed that synaptic transmission at control AC-CA3 ...

TY - JOUR. T1 - Presynaptic kainate receptors regulate spinal sensory transmission. AU - Kerchner, Geoffrey A.. AU - Wilding, Timothy J.. AU - Li, Ping. AU - Zhuo, Min. AU - Huettner, James E.. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Small diameter dorsal root ganglion (DRG) neurons, which include cells that transmit nociceptive information into the spinal cord, are known to express functional kainate receptors. It is well established that exposure to kainate will depolarize C-fiber afferents arising from these cells. Although the role of kainate receptors on sensory afferents is unknown, it has been hypothesized that presynaptic kainate receptors may regulate glutamate release in the spinal cord. Here we show that kainate, applied at low micromolar concentrations in the presence of the AMPA-selective antagonist (RS)-4-(4-aminophenyl)-1,2-dihydro1-methyl-2-propyl-carbamoyl-6,7 -methylenedioxyphthalazine, suppressed spontaneous NMDA receptor-mediated EPSCs in cultures of spinal dorsal horn neurons. In ...

TY - JOUR. T1 - Role of nitric oxide in the hypersusceptibility to pentylenetetrazole-induced seizure in diazepam-withdrawn mice. AU - Tsuda, Makoto. AU - Shimizu, Norifumi. AU - Yajima, Yoshinori. AU - Suzuki, Tsutomu. AU - Misawa, Miwa. N1 - Funding Information: This work was supported in part by a Grant-in-Aid from The Tokyo Biochemical Research Foundation and a Research Grant for Nervous and Mental Disorders from the Ministry of Health and Welfare to T.S. We wish to thank Ms. Sachiko Komiya and Ms. Miho Soma for their expert technical assistance. PY - 1998/2/26. Y1 - 1998/2/26. N2 - The decrease in the seizure threshold for pentylenetetrazole in diazepam-withdrawn mice was not significantly affected by L-arginine (50 and 100 μg/mouse, i.c.v.), which did have an antiseizure effect in chronically vehicle-treated mice. Sodium nitroprusside (25 and 50 μg/mouse, i.c.v.) increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn mice and chronically vehicle-treated mice. ...

How would the cells respond to Aβ? Mancuso injected 5 μL of 10 μM synthetic oligomers into the mouse brain ventricles eight to 10 weeks after transplanting the human microglia. In reaction to this insult, endogenous mouse microglia shifted their transcriptomes sequentially from homeostatic to cytokine responsive, to activated, with the latter partially overlapping with disease-associated microglial (DAM) signatures described previously (Jun 2017 news). Human microglia in the mice underwent a transcriptional transformation as well, but analysis of more than 10,000 orthologous genes indicated poor correlation between human and mouse microglial responses. Of 207 differentially activated genes, 112 were up in human but not mouse microglia; they included GWAS hits BIN1 and PICALM. "We saw that human microglia responded very differently to Aβ oligomers. This emphasizes the need to look specifically at human cells in the context of AD," said De Strooper.. Blurton-Jones and colleagues took a ...

Research into exosomal signaling in the CNS is scant especially with regard to glial cells. However, astrocytes and glioblastomas release exosomes containing mitochondrial DNA [26] and primary mouse microglia, BV2 microglial cells as well as the N9 microglial cell line have been reported to secrete exosomes constitutively [27-29]. We show here that primary rat microglia release exosomes following stimulation with Wnt3a, but exosomes or indeed other proteins are not released under control conditions in our study. This discrepancy with previous findings might reflect the down-regulated nature of our microglia isolated using percoll density gradient centrifugation compared to microglia isolated from mixed glial cultures, or microglial cell lines, which display a heighten activation state due to time spent in culture (unpublished observations: J Pocock). Wnt3a-induced exosomes were approximately 100 nm in diameter; typical of exosomal size. The vesicles aggregated in vitro and harboured ...

HYPOXIC ENCEPHALOPATHY SECONDARY TO STATUS EPILEPTICUS SECONDARY TO CENTRAL NERVOUS SYSTEM INFECTION - Free ebook download as Word Doc (.doc / .docx), PDF File (.pdf), Text File (.txt) or read book online for free. Marie Allexis Campaner February 2011

Schizophrenia is a debilitating and complex mental disorder whose exact etiology remains unknown. There is growing amount of evidence of a relationship between neuroinflammation, as demonstrated by microglial activation, and schizophrenia. Our previous studies have proposed that hyperbilirubinemia plays a role in the pathophysiology of schizophrenia. Furthermore, we suggested the Gunn rat, an animal model of bilirubin encephalopathy, as a possible animal model of schizophrenia. However, the effects of unconjugated bilirubin on microglia, the resident immune cell of the CNS, in Gunn rats have never been investigated. In the present study, we examined how microglial cells respond to bilirubin toxicity in adult Gunn rats. Using immunohistochemical techniques, we compared the distribution, morphology, and ultrastructural features of microglial cells in Gunn rats with Wistar rats as a normal control. We also determined the ratio of activated and resting microglia and observed microglia-neuron interactions.

The excitatory amino acid domoic acid is the causative agent of amnesic shellfish poisoning in humans. The in vitro effects of domoic acid on rat neonatal brain microglia were compared with E. coli lipopolysaccharide (LPS), a known activator of microglia mediator release over a 4 to 24 hour observation period. LPS [3 ng/mL] but not domoic acid [1mM] stimulated a statistically significant increase in TNF-α mRNA and protein generation. Furthermore, both LPS and domoic acid did not significantly affect TGF- β1 gene expression and protein release. Finally, an in vitro exposure of microglia to LPS resulted in statistically significant MMP-9 expression and release, thus extending and confirming our previous observations. However, in contrast, no statistically significant increase in MMP-9 expression and release was observed after domoic acid treatment. Taken together our observations do not support the hypothesis that a short term (4 to 24 hours) in vitro exposure to domoic acid, at a concentration toxic to

Anticonvulsive and neuroprotective effects of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV), a potent agonist for Group II metabotropic glutamate receptors, were examined in vivo against the excitotoxicity of kainic acid in the rat. Intraventricular injection of kainic acid (2 nmol) …

Vigabatrin (VGB) is used for focal seizures in tuberous sclerosis (TS) and may be an effective therapy in patients who fail to respond adequately to other anti-seizure medications while awaiting definitive epilepsy surgery.. Vigabatrin is well-established as the first-line therapy for infantile spasms in association with tuberous sclerosis, but less is known about its role in focal seizures due to tuberous sclerosis.. [Researchers] retrospectively identified 22 patients with tuberous sclerosis who received Vigabatrin for focal seizures, starting Vigabatrin in June 1989 and continuing through the present time. Nineteen (86%) had a history of infantile spasms and all except the two oldest, born in 1986, received Vigabatrin for infantile spasms. Eleven of these individuals exhibited improvement in or resolution of infantile spasms. Sixteen out of 17 with infantile spasms remained on Vigabatrin to treat focal seizures.. The risk for vision loss due to photoreceptor toxicity continues to limit ...

TY - JOUR. T1 - Sigma receptor ligand, (+)-pentazocine, suppresses inflammatory responses of retinal microglia. AU - Zhao, Jing. AU - Ha, Yonju. AU - Liou, Gregory I.. AU - Gonsalvez, Graydon B.. AU - Smith, Sylvia B.. AU - Bollinger, Kathryn E.. N1 - Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 2014/5/8. Y1 - 2014/5/8. N2 - Purpose. To evaluate the effects of the σ 1 receptor (σR1) agonist, (+)-pentazocine, on lipopolysaccharide (LPS)-induced inflammatory changes in retinal microglia cells. Methods. Retinal microglia cells were isolated from Sprague-Dawley rat pups. Cells were treated with LPS with or without (+)-pentazocine and with or without the σR1 antagonist BD1063. Morphologic changes were assayed. Cell viability was assessed by using MTT assay. Supernatant levels of tumor necrosis factor α (TNF-α), interleukin 10, (IL-10), monocyte chemoattractant protein-1 (MCP-1), and nitric oxide (NO) were determined. Reactive oxygen species (ROS) formation was assayed, and ...

Looking for online definition of AMPA-kainate receptor in the Medical Dictionary? AMPA-kainate receptor explanation free. What is AMPA-kainate receptor? Meaning of AMPA-kainate receptor medical term. What does AMPA-kainate receptor mean?

Neurotrophins have long been recognized for their crucial roles in growth, differentiation, and survival in the developing nervous system. Recent findings demonstrating that the pro- form of NGF induces cell death via the p75NTR suggest that the consequences of neurotrophin signaling depend on many factors, in particular the balance between pro- and mature neurotrophins and the regulation of that balance, which may be altered in pathophysiological situations. Since p75NTR is upregulated in many types of neural injury and disease (Park et al., 2000; Troy et al., 2002; Harrington et al., 2004), the increased availability of a ligand that can stimulate apoptotic signaling through this receptor creates an environment in which these neurons are vulnerable. Thus, understanding neurotrophin processing is an important step toward understanding the pathway that a cell takes toward survival or death, especially in disease or after injury. We have detected increased proNGF levels in the CSF following ...

California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis ...

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is predominantly mediated by Y2 receptors, which, together with neuropeptide Y, are upregulated after seizures as a compensatory mechanism. To explore whether such upregulation could prevent seizures, we overexpressed Y2 receptors in the hippocampus using recombinant adeno-associated viral vectors. In two temporal lobe epilepsy models, electrical kindling and kainate-induced seizures, vector-based transduction of Y2 receptor complementary DNA in the hippocampus of adult rats exerted seizure-suppressant effects. Simultaneous overexpression of Y2 and neuropeptide Y had a more pronounced seizure-suppressant effect. These results demonstrate that overexpression of ...

This is the first study that presents concentrations of domoic acid detected in the whole shellfish tissue from breeding and harvesting areas along the Croatian coast of the Adriatic Sea during the period 2006 to 2008. Shellfish sample analyses after SAX cleaning procedures, using a UV-DAD-HPLC system, showed the presence of domoic acid in four species. The most prevalent of those species were the blue mussel (Mytilus galloprovincialis), followed by European flat oyster (Ostrea edulis), Mediterranean scallop (Pecten jacobaeus) and proteus scallop (Flexopecten proteus). Domoic acid, a potentially lethal phycotoxin that causes amnesic shellfish poisoning (ASP), was detected for the first time in January 2006 with the highest value of 6.5486 μg g-1 in whole shellfish tissue. Pseudo-nitzschia spp. bloom events preceded these high domoic acid concentrations. According to this study, retention of domoic acid in the blue mussel M. galloprovincialis is more than 42 days. This investigation indicates the first

The diversity of Pseudo-nitzschia (Bacillariophyceae) and accumulation of the neurotoxin domoic acid (DA) in two types of shellfish; tuberculate cockles (Acanthocardia tuberculata) and sweet clams (Challista chione) was explored in M'diq Bay,Morocco during 2007. The highest abundances of Pseudo-nitzschia were found during the period from March to October, with peaks occurring in May and September. Toxin analysis showed an accumulation of domoic acid in shellfish sampled during spring and autumn. The maximum toxin concentration was 4.9 mg DAg-1 of the whole tissue recorded in sweet clam during spring. Using transmission electron microscopy, thirteen Pseudo-nitzschia species were identified, eight of which are known as producers of domoic acid: P. multistriata, P. cuspidata, P. galaxiae, P. multiseries, P. pseudodelicatissima, P. pungens var. aveirensis, P. calliantha and P. fraudulenta. The five non- toxic species observed were P. subpacifica, P. arenysensis, P. dolorosa, P. subfraudulenta, and ...

Abstract Regarding efficacy of new antiepileptic drugs (AEDs) for seizure control, there are three important clinical questions.Download and Read New Antiepileptic Drugs Epilepsy Research Supplement No 3 New Antiepileptic Drugs Epilepsy Research Supplement No 3 It sounds good when knowing the.Several studies show drugs used to treat AEDS reduce bone density, increase risk of fracture, especially for the up to 50% of users unresponsive to AEDS.Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new onset epilepsy. new AEDs with many of the non-AED drugs.AMR has developed set of analyst tools and data models to supplement.. Research identifies protein that could help patients respond more positively to epilepsy drug therapies.Seizures and epilepsy: Hope through research. for treatment of drug-resistant epilepsy ...

AIMS: Phenobarbital is commonly used to treat status epilepticus in resource-poor countries. Although a dose of 20 mg kg(-1) is recommended, this dose, administered intramuscularly (i.m.) for prophylaxis, is associated with an increase in mortality in children with cerebral malaria. We evaluated a 15-mg kg(-1) intravenous (i.v.) dose of phenobarbital to determine its pharmacokinetics and clinical effects in children with severe falciparum malaria and status epilepticus. METHODS: Twelve children (M/F: 11/1), aged 7-62 months, received a loading dose of phenobarbital (15 mg kg(-1)) as an i.v. infusion over 20 min and maintenance dose of 5 mg kg(-1) at 24 and 48 h later. The duration of convulsions and their recurrence were recorded. Vital signs were monitored. Plasma and cerebrospinal fluid (CSF) phenobarbital concentrations were measured with an Abbott TDx FLx fluorescence polarisation immunoassay analyser (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, USA). Simulations were performed to

Recent studies have suggested that the substance P (tachykinin NK(1)) receptor may be a pharmacological target for the treatment of mood disorders. Here, the effects of electroconvulsive shock on tachykinin NK(1) receptor gene expression in the rat brain was investigated. Rats received either a single electroconvulsive shock or five shocks on alternate days. Quantitative autoradiography with [(125)I]Bolton Hunter-substance P, and in situ hybridisation histochemistry, were used to measure tachykinin NK(1) receptor-binding site densities and mRNA abundance, respectively. Densities of tachykinin NK(1) receptor-binding sites were significantly increased in the cerebral cortex following repeated electroconvulsive shock compared to sham treated animals. Densities remained unchanged in the hippocampus, striatum and amygdala. Neither single nor repeated electroconvulsive shock altered tachykinin NK(1) receptor mRNA in the brain regions examined. Hence, repeated electroconvulsive shock increases tachykinin NK(1)

TY - JOUR. T1 - Protective effect of excitatory amino acids on cold-restraint stress-induced gastric ulcers in mice. T2 - Role of cyclic nucleotides. AU - Chen, Sheng Hsuan. AU - Lei, Hsiao Ling. AU - Huang, Lih Ron. AU - Tsai, Li Hsueh. PY - 2001. Y1 - 2001. N2 - Previous studies have shown that excitatory amino acids (EAAs) and their receptors may play important roles in the mammalian enteric system. In this study, we investigated whether EEAs, including L-glutamate (L-Glu) and subtypes N-methyl-D-aspartate (NMDA), kainic acid (KA), and quisqualic acid (QA), reduce cyclic AMP (cAMP) levels and play a role in protecting gastric lesions in cold-restraint stress (CRS) mice. First, we found that dose-dependent administration of four selected EAAs significantly attenuated the increase of cAMP content and exhibited a protective effect on the development of gastric lesions induced by CRS. Second, CRS treatment exhibited a decrease of cGMP content and an increase of cAMP content with marked ...

TY - JOUR. T1 - The normal genital tract of the female California sea lion (Zalophus californianus). T2 - Cyclic changes in histomorphology and hormone receptor distribution. AU - Colegrove, Kathleen M.. AU - Gulland, Frances M D. AU - Naydan, Diane K.. AU - Lowenstine, Linda J. PY - 2009/11. Y1 - 2009/11. N2 - Changes in reproductive tract histomorphology, and estrogen (ERα) and progesterone receptor (PR) expression throughout the breeding cycle were evaluated in free-ranging stranded female California sea lions (Zalophus californianus). Hormone receptor expression in the ovaries, uterus, cervix, and vagina was evaluated using an immunohistochemical technique with monoclonal antibodies. During a large portion of the cycle, ovaries contained both a corpora lutea (CL) and follicles in varying stages of development. In the periods of pupping and estrus during June and July, and in the spring morphologic features of the endometrium suggested estrogen influence. There were areas of squamous ...

California Sea Lion Photos, Zalophus californianus Photos, California Sea Lion Pictures and Photographs by Professional Natural History Photographer Phillip Colla / Oceanlight.com

Some interneurons of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) that is induced by presynaptic glutamate release when the postsynaptic membrane potential is hyperpolarized. This 'anti-Hebbian' form of LTP is prevented by postsynaptic depolarization or by blocking AMPA and kainate receptors. Although both AMPA and kainate receptors are expressed in hippocampal interneurons, their relative roles in anti-Hebbian LTP are not known. Because interneuron diversity potentially conceals simple rules underlying different forms of plasticity, we focus on glutamatergic synapses onto a subset of interneurons with dendrites in stratum oriens and a main ascending axon that projects to stratum lacunosum moleculare, the oriens-lacunosum moleculare (O-LM) cells. We show that anti-Hebbian LTP in O-LM interneurons has consistent induction and expression properties, and is prevented by selective inhibition of AMPA receptors. The majority of the ionotropic glutamatergic synaptic current in

Fan, Wei. Conditions for activation of group I metabotropic glutamate receptors in rat hippocampus. 2010, University of Zurich, Faculty of Science. ...

Antiepileptic drugs provide neuroprotection in several animal models of brain damage, including those induced by status epilepticus (SE). The mechanisms involved in this action are unknown, but neurotrophic factors such as brain-derived neurotrophic factor (BDNF) may play a role. In this study we investigated the changes in BDNF levels in rats in which SE had been induced by pilocarpine injection (400 mg/kg i.p.) and continued for several hours (unprotected group). In other animals (protected groups), SE was suppressed after 30 min by intraperitoneal injection of either diazepam (10 mg/kg) + pentobarbital (30 mg/kg) or paraldehyde (0.3 mg/kg). In diazepam + pentobarbital-treated rats the hippocampal damage caused by SE was significantly lower (p , 0.05) than in unprotected animals. In addition, 2 and 24 h after pilocarpine injection, the levels of BDNF mRNA were moderately increased in the unprotected group, but 'super-induced' in protected animals, especially in the neocortex and hippocampus. A ...

Childhood absence epilepsy (CAE) is a form of generalized epilepsy syndrome. Clinically these seizures are manifest with a sudden, brief (3-15 second) loss of awareness followed by a quick recovery to baseline. Keppra (levetiracetam) is approved by the U.S. Food and Drug Administration (FDA) to treat partial seizures in adults. It is currently being studied in children with partial seizures. Absence seizures can be difficult to detect clinically, therefore the response to therapy will be determined both by clinical observation and by 24 hour EEG recordings. The researchers hope that with this information they will learn how well it works for the treatment of childhood absence epilepsy and at what dose. This is an open-label, dose-ranging pilot study of levetiracetam in subjects with newly diagnosed childhood absence epilepsy. Approximately 20 patients will be needed to study effectiveness and dose requirements. Subjects must not be on any antiepileptic medication at the time of entry into the ...

Glutamate excitotoxicity has been implicated in the pathophysiology of epilepsy. Systemic injection of kainic acid (KA) in the rat produces an animal model of human temporal lobe epilepsy. We examined the temporal expression of the sodium-dependent n

Dantrolene and nimodipine dramatically reduce the number of activated microglia in the hippocampus and reduce the expression of various pro-inflammatory cytokines. It is not clear from our data whether the anti-inflammatory effects of dantrolene and nimodipine are due to direct action on the microglia themselves or an indirect effect via normalization of neuronal Ca+2 levels. Neurotoxicity of conditioned media from activated microglia is reduced when drugs blocking L-VDCCs or RyRs are applied to the microglia cultures [12-14]. However, the in vivo anti-inflammatory effects of these drugs are not so clear-cut. Following facial nerve transection, nimodipine treatment improves motor neuron survival without reducing microglia activation [53]. However, after ischemic-reperfusion injury, nimodipine does improve behavioral outcomes while concurrently reducing microglia activation [54]. Similarly, in vivo treatment with dantrolene is neuroprotective and improves behavioral outcomes in various in vivo ...

Background Carbon monoxide (CO) synthesized by heme oxygenase 1 (HO-1) exerts antinociceptive effects during inflammation but its role during neuropathic pain remains unknown. Our objective is to investigate the exact contribution of CO derived from HO-1 in the modulation of neuropathic pain and the mechanisms implicated. Methodology/Principal Findings We evaluated the antiallodynic and antihyperalgesic effects of CO following sciatic nerve injury in wild type (WT) or inducible nitric oxide synthase knockout (NOS2-KO) mice using two carbon monoxide-releasing molecules (CORM-2 and CORM-3) and an HO-1 inducer (cobalt protoporphyrin IX, CoPP) daily administered from days 10 to 20 after injury. The effects of CORM-2 and CoPP on the expression of HO-1, heme oxygenase 2 (HO-2), neuronal nitric oxide synthase (NOS1) and NOS2 as well as a microglial marker (CD11b/c) were also assessed at day 20 after surgery in WT and NOS2-KO mice. In WT mice, the main neuropathic pain symptoms induced by nerve injury were

Inhibitory control of local neuronal circuits is critical for prefrontal cortical functioning. Modulation of inhibitory circuits by several neuromodulators has been demonstrated, but the underlying mechanisms are unclear. Neuromodulator effects on synaptic vesicle recycling have received little attention. Controversy also exists whether different pools of synaptic vesicles underlie spontaneous and activity-dependent vesicle recycling. We therefore investigated the effects of kainate receptor activation on GABA release in rat prefrontal neocortex using electrophysiological and styryl dye imaging techniques in acute neocortical slices. Electrophysiological studies demonstrated that activation of kainate receptors increased the frequency, but not the amplitude of miniature IPSCs, suggesting a presynaptic action. Using styryl dye staining and multiphoton excitation microscopy, we visualized vesicular release from inhibitory GABAergic terminals in prefrontal cortical slices and demonstrate that ...

Fragile X syndrome is caused by lack of fragile X mental retardation protein (FMRP) due to silencing of the FMR1 gene. The metabotropic glutamate receptors (mGluRs) in the central nervous system contribute to higher brain functions including learning/memory, mental disorders and persistent pain. The transcription factor cyclic AMP-responsive element binding protein (CREB) is involved in important neuronal functions, such as synaptic plasticity and neuronal survival. Our recent study has shown that stimulation of Group I mGluRs upregulated FMRP and activated CREB in anterior cingulate cortex (ACC), a key region for brain cognitive and executive functions, suggesting that activation of Group I mGluRs may upregulate FMRP through CREB signaling pathway. In this study, we demonstrate that CREB contributes to the regulation of FMRP by Group I mGluRs. In ACC neurons of adult mice overexpressing dominant active CREB mutant, the upregulation of FMRP by stimulating Group I mGluR is enhanced compared to wild-type

Kynurenic acid (KYNA or KYN) is a product of the normal metabolism of amino acid L-tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an antagonist at excitatory amino acid receptors. Because of this activity, it may influence important neurophysiological and neuropathological processes. As a result, kynurenic acid has been considered for use in therapy in certain neurobiological disorders. Conversely, increased levels of kynurenic acid have also been linked to certain pathological conditions. Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig in dog urine, which it was apparently named after. It is formed from L-kynurenine in a reaction catalyzed by the enzyme kynurenine-oxoglutarate transaminase. KYNA has been proposed to act on four targets: As an antagonist at ionotropic AMPA, NMDA and Kainate glutamate receptors in the concentration range of 0.1-2.5 mM. ...

TY - JOUR. T1 - Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. AU - Abe, T.. AU - Sugihara, H.. AU - Nawa, H.. AU - Shigemoto, R.. AU - Mizuno, N.. AU - Nakanishi, S.. N1 - Copyright: Copyright 2004 Elsevier B.V., All rights reserved.. PY - 1992. Y1 - 1992. N2 - A cDNA clone for a new metabotropic glutamate receptor, mGluR5, was isolated through polymerase chain reaction-mediated DNA amplification by using primer sequences conserved among the metabotropic glutamate receptor (mGluR) family and by the subsequent screening of a rat brain cDNA library. The cloned receptor consists of 1171 amino acid residues and exhibits a structural architecture common to the mGluR family, possessing a large extracellular domain preceding the seven putative membrane-spanning segments. mGluR5 shows the highest sequence similarity to mGluR1 among the mGluR members and is coupled to the stimulation of phosphatidylinositol ...

Valproic Acid is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat migraine headaches and schizophrenia. In epileptics, valproic acid is used to control absence seizures, tonic-clonic seizures (grand mal), complex partial seizures, and the seizures associated with Lennox-Gastaut syndrome. Valproic Acid is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain. Valproic Acid dissociates to the valproate ion in the gastrointestinal tract. Valproic acid has also been shown to be an inhibitor of an enzyme called histone deacetylase 1 (HDAC1). HDAC1 is needed for HIV to remain in infected cells. A study published in August 2005 revealed that patients treated with valproic acid in addition to highly active antiretroviral therapy (HAART) showed a 75% reduction in latent HIV infection ...

PROTOCOL ENTRY CRITERIA:. --Disease Characteristics-- Lennox-Gastaut syndrome Slow spike and wave pattern on electroencephalogram At least 60 seizures with atypical absence and drop attacks within 1 month Seizure types allowed in addition to those above: Tonic Tonic-clonic Myoclonic Minor motor Absence of progressive lesion confirmed by computerized tomography or magnetic resonance imaging No change documented by physical exam subsequent to imaging No generalized status epilepticus within 3 months while complying with drug therapy No seizures resulting from progressive disease, e.g.: Active infection Neoplasm Metabolic disorder No anoxic episode requiring resuscitation within 1 year --Prior/Concurrent Therapy--. 1 or 2 concurrent maintenance antiepileptics required At least 6 months since corticotropin At least 60 days since acetazolamide or zonisamide At least 60 days since investigational drug or device No ketogenic diet --Patient Characteristics-- Hematopoietic: No hematological abnormality ...

L-serine-O-phosphate (L-SOP) is the immediate precursor to L-serine in the serine synthesis pathway and is also an agonist at the Group III metabotropic glutamate receptors (mGluRs). L-SOP is produced by the enzyme phosphoserine aminotransferase (PSAT) and metabolized to L-serine by phosphoserine ph …

Strains. Nematodes were grown at 20°C under standard conditions that included uncrowded conditions and the presence of ample food (the Escherichia coli strain OP50). Wild-type nematodes were C. elegans strain N2. Mutant strains were obtained from the Caenorhabditis Genetic Center.. cDNA clones and expression constructs. Using degenerate oligonucleotide primers designed to amplify conserved regions of ionotropic glutamate receptors, we amplified DNA fragments from first-strand mixed-stage C. elegans cDNA that encoded portions of glr-3 and glr-5. These partial gene products were used to screen cDNA libraries at high stringency. After screening ∼106 clones, we obtained several partial cDNAs for each gene, indicating that mRNA encoding these glutamate receptor subunits is present at relatively low levels. Hence, we were unable to isolate full-length cDNAs using this approach. We also searched the published C. elegans genome for genes related in sequence to glr-1, glr-3, andglr-5 and identified ...

Excessive recurrent seizures have been shown to produce epileptic brain damage (EBD), which has been demonstrated by many cases of intractable human epilepsy and the studies of various experimental animal models. Hippocampal sclerosis (HS) or mesial temporal sclerosis (MTS) are typical EBDs and are seen in kainic acid (KA) induced models1-5 and in intractable human temporal lobe epilepsy.6,7 On the other hand, the occurrence of EBD in the dog has been controversial because different reports suggest either no specific pathological findings in several cases of idiopathic epilepsy8-11 or similar findings as HS/MST12-15.. Previously, we studied the canine model of KA-induced complex partial status epilepticus4,5. In those studies, although KA was injected into the unilateral amygdala and the partial seizures of early stage started at the injected amygdala, secondary generalized seizures and contralateral partial seizures with secondary generalized seizures were observed frequently during SE. ...

Chronic pain is a debilitating condition which exacts severe emotional, physical and economic tolls on the millions of people who suffer from it worldwide. Opioids are a mainstay of acute, postoperative and cancer pain therapy, however, their use for the treatment of chronic pain is limited by side effects including analgesic tolerance. Although the mechanisms driving analgesic tolerance are not fully understood, we propose that spinal cord glial cells have a fundamental role in this phenomenon. We hypothesize that acutely, morphine binds to abundant neuronal mu opioid receptors, producing analgesia. Chronically, morphine binds to less abundant microglial mu opioid receptors, enhancing intracellular pathway signaling, protein expression and cell migration, causing proinflammatory factor mediated neuronal sensitization and ultimately analgesic tolerance. In Chapter 3, we demonstrated that in vitro ADP dependent microglial migration can be inhibited by glial modulating agents. In Chapter 4, we ...

TY - JOUR. T1 - Activation of metabotropic glutamate receptors induces an inward current in rat dopamine mesencephalic neurons. AU - Mercuri, N. B.. AU - Stratta, F.. AU - Calabresi, P.. AU - Bonci, A.. AU - Bernardi, G.. PY - 1993. Y1 - 1993. N2 - To investigate the electrophysiological effects of the stimulation of the metabotropic excitatory amino acid receptors, we applied trans-1-amino-cyclopentane-1,3-dicarboxylate, an agonist of this type of receptors, on presumed rat dopamine cells intracellularly recorded in vitro. Trans-1-amino-cyclopentane-1,3-dicarboxylate (3-30 μM, t-ACPD) caused a sustained increase of the spontaneous firing rate and a depolarization. When the membrane potential was held at about the resting level (-50, -60 mV), by the single-electrode voltage-clamp technique, t-ACPD induced an inward current. In 57% of the tested cells the inward current was associated with a decrease of the apparent input conductance. In the remaining cells no obvious changes in membrane ...

Zinc (ionic form Zn2+) is a common trace element in the forebrain, and is especially enriched in the hippocampus, a brain structure important for learning and memory. A large amount of vesicular Zn2+ which is thought to be released upon presynaptic depolarisation is found at synapses formed by the axons of dentate granule cells (GCs), known as mossy fibres (MFs). Zn2+ inhibits NMDA and GABAA receptors (NMDAR and GABAAR) at mono-synaptic inputs between MFs and CA3 pyramidal neurons but its role in synaptic integration in the dentate gyrus remains elusive. Whole-cell recordings were obtained from GCs held in voltage-clamp in acute rat hippocampal slices. One tungsten electrode was positioned in stratum lucidum (SL) of CA3b to activate MFs and another in stratum granulosum (SG) to directly stimulate dentate interneurons. Evoked synaptic currents were blocked by superfusion of the GABAAR antagonist bicuculline implying that they were mediated by GABAARs. In contrast, the AMPA/kainate receptor ...

To monitor changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor distribution in living neurons, the AMPA receptor subunit GluR1 was tagged with green fluorescent protein (GFP). This protein (GluR1-GFP) was functional and was transiently expressed in hippocampal CA1 neurons. In dendrites visualized with two-photon laser scanning microscopy or electron microscopy, most of the GluR1-GFP was intracellular, mimicking endogenous GluR1 distribution. Tetanic synaptic stimulation induced a rapid delivery of tagged receptors into dendritic spines as well as clusters in dendrites. These postsynaptic trafficking events required synaptic N-methyl-D-aspartate (NMDA) receptor activation and may contribute to the enhanced AMPA receptor-mediatedtransmission observed during long-term potentiation and activity-dependent synaptic maturation.. ...

Glutamate is an amino acid that acts as a neurotransmitter in the Central Nervous System. It is associated with neural communication, memory formation, and learning. Glutamate receptors are also implicated in a number of neurodegenerative diseases. Exposure to toxins, old age, congenital predisposition, and brain trauma can trigger glutamate receptor activation and ensuing neurodegeneration. Ionotropic glutamate receptors form the ion channel pore that activates when glutamate binds to the receptor. There are also many subtypes of extracellular glutamate receptors that bind to some chemicals more selectively than to glutamate. Sigma-Aldrich offers monoclonal and polyclonal antibodies that act on glutamate receptors. They are reactive in human, rat, and other species, with various applications.

Mossy cells give rise to the commissural and associational pathway of the dentate gyrus, and receive their major excitatory inputs from the mossy fibers of granule cells. Through these feed-back excitatory connections, mossy cells have been suggested to play important roles in both normal signal pro …

Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation. Glutamate receptors are implicated in a number of neurological conditions. Their central role in excitotoxicity and prevalence in the central nervous system has been linked or speculated to be linked to many neurodegenerative diseases, and several other conditions have been further linked to glutamate receptor gene mutations or receptor autoantigen/antibody activity. ...