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)

Temporal lobe epilepsy is a common form of epilepsy in human adults and is associated with a unique pattern of damage in the hippocampus. The damage includes cell loss of the CA3 and CA4 areas and synaptic growth (sprouting) of mossy fibers in the supragranular layer of the dentate gyrus. Experimental evidence indicates that in adult rats the excitatory amino acid, kainic acid, induces a similar pattern of changes in hippocampal circuitry associated with alterations in perforant path excitation and inhibition. It has been suggested that, in humans, this type of damage may be a result of seizures early in life. In this study we examined the effects of kainic acid-induced status epilepticus on synaptic reorganization and paired-pulse electrophysiology in developing rats and adults. Kainic acid induced more severe seizures in 15-day-old rat pups than in adults. In contrast to adult rats, these seizures did not produce CA3/CA4 neuronal loss, mossy fiber sprouting or changes in paired-pulse excitation or inhibition in the hippocampus of rat pups tested 2-4 weeks after status epilepticus. Our results provide evidence that the immature hippocampus may be more resistant to seizure-induced changes than the mature hippocampus.
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PMID:Resistance of the immature hippocampus to seizure-induced synaptic reorganization. 171 81

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

In this chapter, the pathophysiology and neurochemical pathology of epileptic brain damage is discussed on the basis of an integrative approach in which a comparison is made to cell necrosis resulting from ischemia and hypoglycemia. Two main questions are asked. First, is the brain damage resulting from these three disorders of cerebral energy metabolism similar in distribution and structural characteristics, as previously proposed? Second, is it possible to identify one or several neurochemical events, at the cellular and subcellular level, that qualify as the final common pathways leading to neuronal necrosis? A related question is, will seizures cause structural damage even if they do not critically curtail cellular oxygen supply? A review of the literature and of recent results obtained in animals with long-term recovery following status epilepticus of known duration suggests that although brain damage caused by epilepsy shows some similarities to that incurred due to ischemic and hypoglycemic insults, it is far from identical. In well oxygenated animals with an adequate cardiovascular function, 2 hr of status epilepticus causes moderate neuronal necrosis in the cerebral cortex (layers 3-4), the hippocampus (CA4 and CA1 pyramidal cells), and the thalamus (ventromedial nuclei). In rats, status epilepticus of 30 min duration or longer invariably causes infarction of the substantia nigra (pars reticularis), with some affectation of globus pallidus as well. Notably, CA3 pyramids and dentate neurons are spared, as is the pars compacta of the substantia nigra. Neurochemical events in ischemia, hypoglycemia, and status epilepticus show some striking dissimilarities, yet all three conditions lead to neuronal necrosis. In complete or near-complete ischemia, in which metabolic rate virtually ceases; deterioration of tissue energy state is rapid and extensive, with dramatic loss of ion homeostasis; cellular redox systems are reduced; and acidosis is marked to excessive. In hypoglycemic coma, oxygen consumption continues, albeit at a reduced rate; loss of high energy phosphates is extensive but less than complete, as is loss of ion homeostasis; cellular redox system become oxidized; and acidosis is absent. In epileptic seizures, finally, metabolic rate is markedly enhanced; perturbation of tissue energy state and of ion homeostasis is minimal to small; and acidosis is moderate. Results obtained in experimental animals suggest that neuronal necrosis, when incurred, is unrelated to energy failure and occurs in spite of adequate cellular oxygenation. Four neurochemical events are common to all three conditions discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epileptic brain damage: pathophysiology and neurochemical pathology. 287 25

Increased but transient expression of the proto-oncogene c-fos has been recently reported in metrazol and kindling-induced seizures. Here we tested whether kainic acid-induced status epilepticus may result in a long-term increase of this oncogene. A specific pattern of immunoreactive c-fos material was observed with the development of the seizures. Intense labeling first appeared in the dentate gyrus of the hippocampus and the entorhinal cortex. Pyramidal cell layer CA3, CA4 and CA1 as well as other limbic structures were then positively stained during status epilepticus. In addition, the duration of c-fos expression was different according to the anatomical sites. In the dentate gyrus labeling did not exceed 4-5 h whereas the pyramidal cell layer CA1 exhibited increased c-fos expression for as long as 24 h. Here we propose that c-fos which has been related to growth and differentiation in previous studies, could be involved in processes inducing long-term plastic alterations in the limbic system.
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PMID:Long-lasting and sequential increase of c-fos oncoprotein expression in kainic acid-induced status epilepticus. 313 54

The effects of a hippocampal mossy fiber lesion have been determined on neuronal degeneration and limbic seizures provoked by the subsequent intracerebroventricular administration of kainic acid to unanesthetized rats. Mossy fiber lesions were made either by transecting this pathway unilaterally or by destroying the dentate granule cells unilaterally or bilaterally with colchicine. All control rats eventually developed status epilepticus and each temporally discrete seizure that preceded status epilepticus was recorded from the hippocampus ipsilateral to the kainic acid infusion before the contralateral hippocampus. A mossy fiber lesion of the ipsilateral hippocampus prevented the development of status epilepticus in 26% of subjects and in 52% of subjects seizures were recorded from the contralateral hippocampus before the ipsilateral hippocampus. Unlike electrographic records from other treatment groups, those from rats which had received a bilateral colchicine lesion exhibited no consistent pattern indicative of seizure propagation from one limbic region to another. A bilateral, but not a unilateral, mossy fiber lesion also dramatically attenuated the behavioral expression of the seizures. Regardless of its effects on kainic acid-induced electrographic and behavioral seizures, a mossy fiber lesion always substantially reduced or completely prevented the degeneration of ipsilateral hippocampal CA3-CA4 neurons. This protective effect was specific for those hippocampal neurons deprived of mossy fiber innervation. Neurons in other regions of the brain were protected from degeneration only when the mossy fiber lesion also prevented the development of electrographic status epilepticus. These results suggest that the hippocampal mossy fibers constitute an important, though probably not an obligatory, link in the circuit responsible for the spread of kainic acid seizures. Degeneration of CA3-CA4 neurons appears to depend upon (1) the duration of hippocampal seizure activity and (2) an as yet undefined influence of or interaction with the mossy fiber projection which enhances the neurodegenerative effect of the seizures.
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PMID:Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration. 320 Apr 28

To analyze the relation between kainic acid-induced limbic seizures and the associated brain lesions, various doses of kainic acid (117-940 pmol) were administered intracerebroventricularly to unanesthetized rats. Rats which experienced status epilepticus developed lesions in several limbic, neocortical and thalamic regions. However, rats which experienced only temporally discrete seizures (less than 30 min each) suffered neuronal degeneration exclusively in the CA3-CA4 area ipsilateral to the kainic acid infusion, even when other regions exhibited the same total electrographic seizure duration. These results can best be explained by postulating that, in addition to evoking seizures, kainic acid also enhances the toxic effects of seizures on CA3-CA4 neurons.
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PMID:On the relation between seizures and brain lesions after intracerebroventricular kainic acid. 334 75

Neuronal necrosis in the brain resulting from status epilepticus of 15 to 120 minutes duration in ventilated and well-oxygenated rats was assessed. Seizures were induced by inhalation of the convulsant gas flurothyl, and terminated by withdrawal of flurothyl and a single injection of thiopental. The animals were allowed to recover for one week, and neuronal damage was assessed by cell counts following subserial sectioning of the brain and microscopical examination of the sections. Infarction of the pars reticulata of the substantia nigra occurred in 5 of the 6 animals with seizure duration of 30 minutes, and in all animals with longer seizure durations. There also was a common affectation of the central parts of the globus pallidus. The pars compacta of the substantia nigra was never affected. After 45 to 120 minutes of seizures, moderate neuronal necrosis was observed in the neocortex (layers 3 and 4), and after 60 to 120 minutes was seen in amygdaloid and thalamic nuclei, as well as in CA4 and CA1 hippocampal pyramidal cells. Notably, CA3 neurons were not damaged nor were dentate granule cells affected. After 120 minutes of seizures, damage regularly affected the neocortex and the ventral-posterior nuclei of the thalamus. A conspicuous feature was the localization of neuronal necrosis at sites close to the ventricles.
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PMID:Status epilepticus in well-oxygenated rats causes neuronal necrosis. 405 57

In the present investigation we address the question of whether one of the responses to increased neuronal activity is a modification of the expression of the different subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptors (GluR-1, GluR-2, GluR-3). Thus, we used two different models of generalized status epilepticus, as widespread elevated neuronal activity, to study in vivo responses of the AMPA receptor mRNA expression in rat forebrain. By Northern blot analysis and in situ hybridization, we show that one of the delayed responses to LiCl/pilocarpine-induced status epilepticus is a dramatic change in the mRNA level of some subunits of AMPA-selective glutamate receptors. These effects, which appear between 6 and 12 h after the drug treatment, are subunit and brain region specific. The most striking example of differential expression of the three examined GluR mRNAs can be observed in the dentate gyrus of the hippocampus. In this specific brain subregion an increase of GluR-3 mRNA level is induced 12 h after LiCl/pilocarpine treatment, while a clear decrease in GluR-1 mRNA level and no significant change in GluR-2 mRNA level can be observed in the same area under these experimental conditions. Both the GluR-1 decrease and the GluR-3 increase are transient effects and a return to basal level can be observed after 48-72 h. In the CA1 layer of the hippocampus, a parallel decrease of both GluR-1 and GluR-3 expression is found 12-24 h after drug treatment, followed by a recovery of the expression to control values at 48 h. In kainate-induced epilepsy we could reproduce the late increase (12-24 h) in GluR-3 mRNA in the dentate gyrus; however, under this experimental condition, no clear decrease of GluR-1 expression can be observed in this area. A general decrease in mRNA level for the AMPA receptor subunits (GluR-1-3) in the hippocampal layers, in particular in CA3 and CA4 subfields, was also observed. In conclusion the results reported in the present paper reveal a specific regulation of GluR gene expression in the granule cells of the hippocampal dentate gyrus and stimulate further investigation on the functional role of the GluR-3 subunit in the receptor-channel complex.
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PMID:Changes in gene expression of AMPA-selective glutamate receptor subunits induced by status epilepticus in rat brain. 752 10

In adult rats, intraperitoneal administration of kainic acid, a glutamic acid analog and potent neurotoxin, induces persistent seizure activity that results in electrographic alterations and neuropathology that closely resemble human temporal lobe epilepsy. We used in situ hybridization to identify regions of altered glutamate and GABAA receptor gene expression following kainate-induced status epilepticus. In the CA3/CA4 area, the hippocampal region most vulnerable to neurodegeneration after kainate acid treatment, expression of GluR2 (the AMPA/kainate receptor subunit that limits Ca2+ permeability) and GluR3 was decreased markedly at 12 and 24 hr, times preceding neurodegeneration. These findings raise the possibility that increased formation of Ca(2+)-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABAA alpha 1, subunit was also reduced, indicating a possible decrease in inhibitory transmission, which would also enhance excitotoxicity. GluR1 and NR1 expression was not significantly changed. In the dentate gyrus, a region resistant to neurodegeneration, concomitant increases in GluR2 and GluR3 expression were observed; GluR1, NR1, and GABAA alpha 1 mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABAA alpha 1 expression represented changes in mRNA content per neuron and were specific to pyramidal cells of the CA3/CA4 area and to granule cells of the dentate gyrus. These findings indicate that kainate seizures modify hippocampal glutamate and GABAA receptor expression in a cell-specific manner. Timing of the changes in glutamate and GABAA receptor mRNAs indicates that these changes may play a causal role in hippocampal neuronal cell loss following kainate-induced seizures.
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PMID:Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus: an in situ hybridization study. 818 36

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


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