Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neural cell adhesion molecule (NCAM) changes at the cell surface during development, from highly sialylated forms (embryonic or E-NCAM) to three size classes of less sialylated proteins with apparent molecular mass of 180, 140, and 120 kDa (adult NCAM). In the nervous system, E-NCAM has been localized in developing tissues, where it is thought to play a role in the structuring of neuronal groups and tissue pattern formation. In the present study a monoclonal antibody that specifically detects E-NCAM was used in immunoblot and immunohistochemical procedures. In developing rat hippocampus, E-NCAM cell expression was found to change according to a precise pattern and persisted until 1 month after birth. It was closely associated with the mossy fiber system, an area known for its sprouting propensity. In adult rats, although immunoreactivity considerably decreases and becomes undetectable by immunoblot analysis, E-NCAM was still found to be associated with a few pyramidal-shaped cells in the innermost part of the dentate gyrus. In order to acquire some insight into potential histogenetically plastic functions of E-NCAM, in another series of experiments adult rats were treated with kainic acid, a powerful excitotoxic and convulsant glutamate analog eliciting status epilepticus. When these animals were examined for E-NCAM expression, an intense labeling was found associated with glial-like cells, particularly in the hippocampal formation, and corresponding approximately to the reactive gliosis, as confirmed by staining with anti-glial fibrillary acidic protein antibodies. This expression was detectable from about 3 d following kainic acid administration and persisted for at least 12 weeks; it developed according to an observable spatiotemporal distribution pattern. In animals submitted to amygdala kindling, a nonlesional model of secondarily generalized epilepsy, no such reexpression of E-NCAM was observed. Our observations imply that polysialylation may be a means of identifying neuronal structures capable of plasticity in the CNS. Moreover, intense reexpression of E-NCAM could be a marker of reactive gliosis following brain damage.
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PMID:The embryonic form of neural cell surface molecule (E-NCAM) in the rat hippocampus and its reexpression on glial cells following kainic acid-induced status epilepticus. 154 43

Autopsy study of a patient who died after an episode of prolonged unilateral status epilepticus revealed neuronal loss in the hippocampus on the epileptic side, with gliosis confined to the CA1 and CA3 fields. There was loss of the parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)-ergic interneurons in the hippocampus on that side. There was also loss of the normal laminar pattern of substance P staining with increased substance P immunoreactivity in the supragranular plexus on that side. Met-enkephalin immunoreactivity was also increased in the outer molecular layer of the dentate gyrus on the epileptic side. Mossy fibers on the epileptic side stained more strongly with the Hicks' silver stain and with antibodies against glutamate and taurine, but less intensely with antibodies against calbindin. In the contralateral cerebellum, there was Purkinje cell loss, injury to the remaining Purkinje cells, and increased prominence of the Bergmann glia. Our observations show that prolonged unilateral seizure activity can be associated with specific histochemical changes in the human hippocampus.
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PMID:Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus. 171 86

Expression of heat shock proteins (HSPs) occurs in brain after ischemia and status epilepticus. We report that induction of the heat shock response in cortical cultures protects neurons from glutamate-induced excitotoxicity. Cultures heated to 42.2 degrees C for 20 min showed an overall decrease in protein synthesis but an increase in the synthesis of approximately 72 and approximately 85 kd proteins and in the levels of HSP70 mRNA. Heat shock inhibited excitotoxicity in cells exposed to glutamate at 3 or 24 hr following heat exposure, but not when the interval between heat and glutamate exposure was shortened to 15 min or lengthened to 48 hr. Protection due to heat shock required new protein synthesis, since it did not occur when protein or RNA synthesis inhibitors were added. By ameliorating excitotoxic processes, HSPs may attenuate brain injury in certain pathologic conditions.
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PMID:Heat shock protects cultured neurons from glutamate toxicity. 172 11

Domoate, a glutamate analog, is believed to be responsible for a seafood poisoning incident that caused acute neurological disturbances and chronic memory impairment in some victims, with the incidence of mortality and neuropsychological morbidity being highest among the aged. Domoate expresses neurotoxic (excitotoxic) activity in vitro by an action at the kainate subtype of glutamate receptor, and when administered to adult rats, it mimics kainate in causing status epilepticus and a severe seizure-brain damage syndrome. Because domoate is exceedingly expensive, we explored the feasibility of using kainate to study the age-linked features of domoate neurotoxicity. We administered kainate subcutaneously in various doses to young (5-6 months), middle-aged (12-13 months), and old (22-25 months) rats and found the middle-aged and old rats significantly more sensitive than young rats to the neurotoxic actions of kainate. Low doses of kainate, which were nontoxic to young rats, frequently triggered status epilepticus, associated brain damage, and precipitous death in old rats. Middle-aged rats were more sensitive than young rats, but less sensitive than old rats to kainate neurotoxicity. These results suggest that the kainate-treated rat may be a useful model for studying mechanisms underlying age-related aspects of the human domoate neurotoxic syndrome.
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PMID:Age-related sensitivity to kainate neurotoxicity. 174 99

The excitatory amino acid glutamate plays an important role in the mammalian CNS. Studies conducted from 1940 to 1950 suggested that oral administration of glutamate could have a beneficial effect on normal and retardate intelligence. The neurotoxic nature of glutamate resulting in excitotoxic lesions (neuronal death) is thought possibly to underlie several neurological diseases including Huntington's disease, status epilepticus. Alzheimer's dementia and olivopontocerebellar atrophy. This neurodegenerative effect of glutamate also appears to regulate the formation, modulation and degeneration of brain cytoarchitecture during normal development and adult plasticity, by altering neuronal outgrowth and synaptogenesis. In addition to its function as a neurotransmitter in several regions of the CNS, glutamate seems to be specifically implicated in the memory process. Long-term potentiation (LTP) and long-term depression (LTD), two forms of synaptic plasticity associated with learning and memory, both involve glutamate receptors. Studies with antagonists of glutamate receptors reveal a highly selective dependency of LTP and LTD on the N-methyl-D-aspartate and quisqualate receptors respectively. The therapeutic value of glutamate receptor antagonists is being actively investigated. The most promising results have been obtained in epilepsy and to some extent in ischaemia and stroke. The major drawback remains the inability of antagonists to permeate the blood-brain barrier when administered systemically. Efforts should be directed towards finding antagonists that are lipid soluble and able to cross the blood-brain barrier and to find precursors that would yield the antagonist intracerebrally.
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PMID:Glutamate in the mammalian CNS. 198 Nov 50

Status epilepticus (SE) evolves through several stages when untreated. The later stages of SE are less responsive to standard anticonvulsants and may require general anesthesia to suppress seizures. Antagonists acting at the N-methyl-D-aspartate (NMDA) subclass of glutamate (excitatory) receptors have been demonstrated to exert antiepileptic activity in some seizure models. We report experiments performed to determine if NMDA receptor antagonists are effective in stopping seizures in the late stages of SE. A model of limbic SE induced by 90 min of 'continuous' electrical stimulation of the hippocampus in rats was employed. Three NMDA receptor antagonists, one 'competitive' (CPP) and two 'non-competitive' (ketamine and MK-801), were compared to 3 standard antiepileptic drugs (diazepam, phenobarbital, and phenytoin) for their ability to suppress seizures at a physiologically defined stage of SE. All NMDA receptor antagonists, diazepam and phenobarbital were effective in suppressing behavioral and electrographic seizures for varying periods of time. Phenytoin had no effect on SE. Ketamine and MK-801 induced a paradoxical enhancement of electrographic seizures that preceded SE suppression. We believe that NMDA-receptor antagonists offer a novel approach for treating the late stages of SE.
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PMID:NMDA receptor antagonists and limbic status epilepticus: a comparison with standard anticonvulsants. 216 58

A recent outbreak of human food poisoning, characterized by severe gastrointestinal and neurologic abnormalities, with a fatal outcome in 3 patients, was attributed to the consumption of poisonous mussels containing domoic acid at an abnormally high concentration. The purpose of the present study was to determine if domoic acid, a glutamate analogue extracted from poisonous mussel, was neurotoxic to rats. Groups of female Sprague-Dawley rats were dosed once intraperitoneally with 0, 1, 2, 4, or 7.5 mg domoic acid/kg of body weight and observed for a maximum period of 24 hr. Clinically, control rats and rats in the 1 mg/kg group were unremarkable. Seventy-five percent of the animals in the 2 mg/kg group had equivocal transient behavioral signs. One that was given 2 mg/kg and all rats given in excess of 4 mg/kg of body weight developed unequivocal behavioral and neurologic signs culminating in partial seizures and status epilepticus. Histopathologically, severely affected rats developed selective encephalopathy characterized by neuronal degeneration and vacuolation of the neuropil in the limbic and the olfactory systems, and retinopathy characterized by neuronal hydropic degeneration of the inner nuclear layer and vacuolation of the external plexiform layer. The results of this study suggest that domoic acid is excitotoxic and causes a characteristic syndrome with clinical signs and histopathologic lesions similar to those reported for kainic acid.
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PMID:Acute neurotoxicity of domoic acid in the rat. 236 84

Glutamate is the putative neurotransmitter of several clinically important pathways, including cortical association fibers, corticofugal pathways such as the pyramidal tract, and hippocampal, cerebellar, and spinal cord pathways. The excitatory actions of glutamate are mediated by multiple, distinct receptor types and potent receptor antagonists have recently been developed. Glutamate also has neurotoxic properties and can produce "excitotoxic" lesions reminiscent of human neurodegenerative disorders. Abnormally enhanced glutamatergic neurotransmission may cause excitotoxic cell damage and lead to the neuronal death associated with olivopontocerebellar atrophy, Huntington's disease, status epilepticus, hypoxia/ischemia, and hypoglycemia. Pharmacologic manipulation of the glutamatergic system may have great potential for the rational treatment of a variety of neurologic diseases.
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PMID:The role of glutamate in neurotransmission and in neurologic disease. 242 40

Glutamate, the major excitatory neurotransmitter of the brain, mediates neuronal injury from hypoxia-ischemia, hypoglycemia, and status epilepticus. Drugs that block glutamate receptors, particularly the N-methyl-D-aspartate (NMDA) receptor, protect neurons from these insults. Noncompetitive antagonists of NMDA receptors have the potential to prevent perinatal neurologic morbidity.
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PMID:Role of excitatory amino acids in brain injury caused by hypoxia-ischemia, status epilepticus, and hypoglycemia. 254 4

Pathological conditions which interfere with normal brain energy metabolism causes similar neuronal degeneration. Cerebral ischemia, hypoglycemia, and status epilepticus are well known examples of such disease processes. Recently, it has come to be realized that the similarity of the pattern of neuronal degeneration is probably due to the toxicity of a putative neurotransmitter glutamate. Ischemic hippocampal damage in rodents has been studied as a typical experimental model. Following brief ischemia, the rodent hippocampus recovers completely and then starts degenerating over a few days. The delayed neuronal death of the hippocampus could be accounted for by excitotoxic action of glutamate. There is a considerable body of evidence to support this hypothesis. Extracellular glutamate actually increases following brief ischemia. Preceding destruction of glutamatergic input to the hippocampal CA1 (deafferentation) partially prevents ischemic neuronal damage in CA1. Various drugs are reportedly effective in preventing ischemic CA1 damage and some of them have a property of glutamate antagonist. However, why glutamate brings about cell necrosis is still not fully understood. Further study of basic mechanism is awaited.
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PMID:[Neuronal degeneration and glutamate]. 257 28


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