Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accumulation of the stress protein HSP70 was found to be an excellent marker for prolonged seizure related metabolic activity of neurons. After kainic acid (KA) induced status epilepticus we observed HSP70 immunoreactivity in the hippocampal CA4 and CA1 sectors, the subiculum, the basolateral and the lateral nuclei of the amygdala, the mediodorsal nucleus of the thalamus, the caudal part of the striatum, the claustrum and in neurons of certain neocortical areas. HSP70-positive nerve cells appeared normal in conventional histological stains. Conversely, degenerating neurons (e.g. in the hippocampal CA3 sector) remained unlabeled.
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PMID:Induction of stress protein HSP70 in nerve cells after status epilepticus in the rat. 276 75

The transcription factor KROX-20, unlike many other immediate early genes, is not expressed in the rat hippocampus after bicuculline induced generalized seizures. Since limbic seizures are a more injurious stimulus, the KROX-20 expression profile was investigated in adult rats subjected to kainic acid induced limbic epilepsy at postictal intervals up to 48 h. Immunocytochemistry was performed using a specific polyclonal antiserum. In the hippocampus a sequential induction was observed with peak levels attained in dentate gyrus at 3 h, in CA1 at 8 h and in CA3 between 8 and 24 h, respectively. In contrast, no KROX-20 induction was found in hilus neurons. Prominent neuronal KROX-20 induction was also detected in other areas of the limbic system, in particular in amygdala and piriform cortex, as well as non-limbic regions such as neocortex and striatum. As is the case with KROX-20, heat shock protein (HSP) 70, a reliable marker for reversible neuronal injury, has a high induction threshold. Though not inducible in the hippocampus by generalized seizures, it is expressed after limbic epilepsy. Therefore, co-expression of KROX-20 and HSP70 was studied by a double labeling technique using a monoclonal antibody directed against the inducible form of HSP70. Neuronal subpopulations with perfect co-expression such as hippocampal CA1 neurons contrasted with others demonstrating partial co-induction (cortical neurons) or lack of co-expression (hilus cells), indicating that different stimuli trigger the activation of these two inducible genes.
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PMID:High induction threshold for transcription factor KROX-20 in the rat brain: partial co-expression with heat shock protein 70 following limbic seizures. 809 69

The c-fos immediate early gene is induced by normal stimuli including light, stress, hyperosmolar solutions, and hormones. Ischemia, hypoxia, seizures, cortical injury, nerve section and other pathological stimuli can also induce c-fos. The induction can occur via increases in intracellular calcium that act through a Ca2+/cAMP element on its promoter, or via trophic and other factors that act through a serum response element (SRE) on its promoter. Several studies show that calcium entry via voltage sensitive calcium channels (VSCCs) is important for inducing c-fos. We have shown that calcium entry via the NMDA receptor is important for induction of c-fos mRNA by glutamate and cAMP in cultured cortical neurons. Moreover, the NMDA receptor appears to regulate translation of c-fos mRNA to Fos protein when cells are stimulated with other types of stimuli including vasoactive intestinal peptide, zinc, and fibroblast growth factor. These results suggest that toxins that elevate intracellular calcium will likely induce the c-fos gene in brain. The heat shock or stress genes are induced by a wide variety of stimuli including heavy metals, heat, oxidative and ischemic stress, prolonged seizures, hypoglycemia, calcium ionophores, and certain toxins. It is believed that denatured proteins stimulate heat shock factors to bind to heat shock elements on the promoters of all heat shock genes to induce gene transcription. We and others have shown that global and focal ischemia induce the hsp70 heat shock gene in brain. Mild ischemia induces hsp70 mRNA and HSP70 protein in neurons only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in gene expression as an index of neuronal injury: heat shock and the immediate early gene response. 809 Mar 62

The effects of electroconvulsive seizure and anti-convulsant drugs on induction of mRNA of heat shock protein were studied in mouse brain. Electrical shock induced mRNA of heat shock cognate protein (HSC70), but not heat shock protein (HSP70) mRNA. The induction was maximum 1 h after the ECS and continued for several hours, followed by long-lasting depression. Diazepam slightly prevented the ECS, but strongly attenuated the induction of HSC70 mRNA. Whereas phenytoin, which blocked the seizure, did not decrease but delayed the induction of HSC70 mRNA. The present results suggest that HSC70 mRNA level is increased with the ECS and that the induction level did not necessarily correlate the severity of the seizure.
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PMID:Correlation between electroconvulsive seizure and HSC70 mRNA induction in mice brain. 823 52

The hsp70 gene is induced by denatured protein in injured cells and is an extremely sensitive and reliable marker of cells injured by ischemia, seizures, and toxins. Normal brains have little detectable hsp70 mRNA or HSP70 protein. After status epilepticus produced by systemic injections of kainic acid, however, HSP70 protein is induced in neurons but not glia in brain regions known to be injured by kainic acid. Global and focal ischemia also induce the hsp70 gene in brain. The induction of HSP70 protein in hippocampus following increasing durations of global ischemia correlates with the regional and cellular vulnerability to ischemia: CA1 neurons express HSP70 after the briefest periods of ischemia followed by CA4, CA3, dentate granule neurons, glia, and lastly, endothelial cells. Moreover, as the severity of ischemia worsens, a transcriptional and/or translational blockade of the hsp70 gene occurs in the same order so that moderate degrees of ischemia induce HSP70 in CA3 neurons and dentate granule neurons but not necrotic CA1 neurons, and severe ischemia induces HSP70 in capillary endothelial cells of hippocampus but not in any infarcted neurons or glia throughout the hippocampus. Brief periods of focal ischemia induce HSP70 primarily in neurons, suggesting that even focal ischemia can produce selective neuronal injury without infarction. In some instances, HSP70 immunoreactive astrocytes surround the HSP70 immunostained neurons. Focal ischemia that produces infarction induces HSP70 primarily in endothelial cells of cerebral blood vessels in the regions of infarction and in neurons and astrocytes on the perimeter or the penumbral area of infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HSP70 heat shock gene regulation during ischemia. 824 24

The effect of MK-801, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, on the kainic acid-induced expression of the inducible heat shock protein 70 kDa (HSP70) and on neuronal death in the rat hippocampus was investigated. HSP70 is expressed in approximately 80% of the pyramidal neurons in the CA1 field 1 day after kainic acid injection. The majority of these HSP70-immunopositive neurons exhibited swelling and a hollow appearance in the perikaryon, indicating that they had been injured following kainic acid-elicited limbic seizures. Four days after administration of kainic acid, 87% of the pyramidal neurons in the CA1 field were dead. When a single dose of MK-801 was administered 1 h before kainic acid injection, the number of rats suffering with seizures was reduced, the severity of limbic seizures was attenuated and seizure onset was delayed. Neither HSP70 expression on day 1 nor neuronal loss on day 4 in the CA1 pyramidal cell layer was observed in these animals. A considerable number of HSP70-immunopositive neurons was detected in the dentate hilus, however, and somewhat fewer in the CA3a and CA3c subfields on day 1. Severe neuronal damage in these regions followed on day 4. Interestingly, little HSP70 expression or neuronal loss was observed in the CA3b subfield in these same animals. When a single dose of MK-801 was given 4 h after kainic acid treatment, HSP70 expression was partially blocked; 18% of neurons expressed HSP70 on day 1 and 37% on day 4 in CA1 pyramidal neurons in comparison to the kainic acid controls. About 50% neuronal death was detected in the CA1 pyramidal cell layer 4 days after kainic acid treatment followed by MK-801. When the animals were treated with MK-801 4 h after kainic acid treatment followed by additional daily administration for 3 days, a negligible number of pyramidal neurons expressed HSP70, and the survival of pyramidal cells was significantly increased in the CA1 field. Limbic seizure-induced HSP70 expression not only indicates neuronal injury in the pyramidal cell layer of the hippocampus but also predicts delayed neuronal death, at least in the case of the CA1 field of animals that suffered stage IV-V seizures.
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PMID:Expression of heat shock protein-70 and limbic seizure-induced neuronal death in the rat brain. 875 50

Food restriction can extend life span in rodents and was recently reported to increase the resistance of neurons in the brain to excitotoxic and metabolic insults. In principle, administration to ad libitum fed rodents of an agent that reduces glucose availability to cells should mimick certain aspects of food restriction. We now report that administration of 2-deoxy-D-glucose (2DG), a non-metabolizable analog of glucose, to adult rats results in a highly significant reduction in seizure-induced spatial memory deficits and hippocampal neuron loss. Pretreatment of rat hippocampal cell cultures with 2DG decreases the vulnerability of neurons to excitotoxic (glutamate) and oxidative (Fe2+) insults. The protective action of 2DG is associated with decreased levels of cellular oxidative stress and enhanced calcium homeostasis. 2DG treatment increased levels of the stress-responsive proteins GRP78 and HSP70 in hippocampal neurons, without affecting levels of Bcl-2 or GRP75, suggesting that mild reductions in glucose availability can increase neuronal resistance to oxidative and metabolic insults by a mechanism involving induction of stress proteins. Our findings establish cell culture and in vivo models of "chemical food restriction" which may prove useful in elucidating mechanisms of neuroprotection and in developing preventive approaches for neurodegenerative disorders that involve oxidative stress and excitotoxicity.
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PMID:2-Deoxy-D-glucose protects hippocampal neurons against excitotoxic and oxidative injury: evidence for the involvement of stress proteins. 1039 35

In response to many environmental and pathophysiologic stressful stimuli, cells undergo a stress response characterized by induction of a variety of proteins, including the heat shock protein family. The inducible heat shock protein 70 (hsp70) is believed to participate in an array of cellular activities, including cytoprotection. Normal brain cells have little detectable hsp70 RNA or protein. However, following a stressful condition hsp70 mRNA and protein are induced in different cell types depending on the severity and the nature of the stimulus. The induction of hsp70 protein correlates with the regional and cellular vulnerability to a particular injury as identified by standard histologic methods. The pattern of hsp70 expression differs in response to various neurotoxic stimuli, including hyperthermia, ischemia, seizures, hemorrhage, and N-methyl-D-aspartate receptor antagonist administration. Hsp70 expression is a useful marker of cellular injury and may help to identify previously unrecognized areas of vulnerability in the nervous system after a neurotoxic stimulus. Hsp70 may also play a neuroprotective role in the brain.
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PMID:Stress proteins as molecular markers of neurotoxicity. 1066 96

The ability of the sulfonylurea receptor (SUR) 1 to suppress seizures and excitotoxic neuron damage was assessed in mice transgenically overexpressing this receptor. Fertilized eggs from FVB mice were injected with a construct containing SUR cDNA and a calcium-calmodulin kinase IIalpha promoter. The resulting mice showed normal gross anatomy, brain morphology and histology, and locomotor and cognitive behavior. However, they overexpressed the SUR1 transgene, yielding a 9- to 12-fold increase in the density of [(3)H]glibenclamide binding to the cortex, hippocampus, and striatum. These mice resisted kainic acid-induced seizures, showing a 36% decrease in average maximum seizure intensity and a 75% survival rate at a dose that killed 53% of the wild-type mice. Kainic acid-treated transgenic mice showed no significant loss of hippocampal pyramidal neurons or expression of heat shock protein 70, whereas wild-type mice lost 68-79% of pyramidal neurons in the CA1-3 subfields and expressed high levels of heat shock protein 70 after kainate administration. These results indicate that the transgenic overexpression of SUR1 alone in forebrain structures significantly protects mice from seizures and neuronal damage without interfering with locomotor or cognitive function.
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PMID:Mice transgenically overexpressing sulfonylurea receptor 1 in forebrain resist seizure induction and excitotoxic neuron death. 1124 15

APG-2 belongs to the heat shock protein 110 family. Although kainic acid (KA)-induced seizures are known to elicit expression of inducible heat shock protein 70 (HSP70) in the brain, no investigation has been carried out on the APG-2 level after excitatory amino acid-induced seizures. By means of an immunoblot assay, we determined the levels of HSP70 and APG-2 in discrete brain structures of mice after a single intraperitoneal injection of KA or N-methyl-D-aspartic acid (NMDA). APG-2 level was significantly decreased in frontal cortex, hippocampus, and striatum three days after the administration of KA, while HSP70 level was increased in these regions following the administration. In any of these regions, APG-2 levels were returned to the control levels 10 days after the administration. However, no significant changes were observed in levels of both HSP70 and APG-2 in hypothalamus, midbrain, medulla-pons, and cerebellum of the mice. By contrast, NMDA administration did not significantly affect both levels in any of the regions examined. These findings indicate that the transient decrease in APG-2 expression is one of the intracellular events elicited by signals peculiar to KA, but not by those peculiar to NMDA, in telencephalon of murine brain.
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PMID:Decrease in level of APG-2, a member of the heat shock protein 110 family, in murine brain following systemic administration of kainic acid. 1152 19


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