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 two forms of epileptic brain damage, that found in patients with chronic epilepsy (post-mortem or in an anterior temporal lobectomy specimen) and that occurring acutely after status epilepticus, have much in common but are not identical. Hippocampal lesions occurring acutely after status epilepticus show a high degree of selectivity for hilar interneurones, CA1 pyramidal neurones and CA3 pyramidal neurones. Hippocampal lesions in anterior temporal lobectomy specimens tend to involve the subfields less selectively with CA1 being only slightly more severely affected than dentate granule cells, CA3 and CA2 pyramidal neurones. The most severely damaged hippocampi may result from a combination of acute damage early in life (commonly from prolonged febrile convulsions) and cumulative damage associated with seizures. Less severe degrees of damage are probably a consequence of repeated seizures. The abnormal patterns of firing associated with epileptic activity are almost certainly responsible for cell death occurring acutely after status epilepticus; they may contribute to the progressive cell loss occurring in chronic epilepsy.
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PMID:Excitotoxicity and epileptic brain damage. 179 Jul 73

Distant damage, localized in the CA3 and CA1 areas, was observed in the hippocampus of rats as a consequence of status epilepticus (SE) induced by the injection of 2.5 nmol of kainic acid (KA) into the amygdala. In animals pretreated with an intraperitoneal injection of the non-competitive antagonist of the N-methyl-D-aspartate receptor, N-[1-(2-thienyl)cyclohexyl]-piperidine (TCP) (20 mg/kg), distant neuronal damage was reduced (CA1 neurons were always spared) whereas the rats still developed SE with an earlier onset. These results demonstrate the protective effect of TCP and confirm that epileptic activity and brain damage may be dissociated by NMDA receptor antagonists.
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PMID:N-[1-(2-thienyl)cyclohexyl]-piperidine (TCP) does not block kainic acid-induced status epilepticus but reduces secondary hippocampal damage. 202 18

The role of the ventral hippocampal dentate granule neurons in the mu opioid receptor agonist-induced motor seizures and wet dog shakes was examined in this study. [NMe-Phe3-D-Pro4]morphiceptin (9.4 nmol) was injected into the left ventral hippocampus of rats 14 days after unilateral or bilateral colchicine (5 nmol/site) lesions of ventral hippocampal dentate granule cells and the subsequent behavioral and neuropathological responses were observed. [NMe-Phe3-D-Pro4]morphiceptin injected into control animals produced convulsions and numerous wet dog shakes that lasted for less than 1 h. [NMe-Phe-D-Pro4]morphiceptin-induced wet dog shakes were significantly reduced in unilateral colchicine-pretreated rats, and completely inhibited in bilateral colchicine-pretreated animals. In contrast, generalized motor seizures evoked by [NMe-Phe3-D-Pro4]morphiceptin were potentiated and prolonged in colchicine-pretreated animals as status epilepticus (sustained clonus of forepaws and head for more than 1 h) was observed in both unilateral and bilateral colchicine-pretreated animals but not in control rats. No morphological damage of granule or pyramidal cells was found in the ventral hippocampus of control animals following [NMe-Phe3-D-Pro4]morphiceptin injection. Colchicine treatment by itself produced a selective lesion of dentate granule cells. In colchicine-pretreated animals, [NMe-Phe3-D-Pro4]morphiceptin induced widespread seizure-related damage of CA3/CA1 pyramidal cells. These results suggest that dentate granule cells in the ventral hippocampus are essential for the elaboration of wet dog shakes. However, these neurons may play an inhibitory role in the spread of seizure activity within the hippocampus or limbic structures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ventral hippocampal dentate granule cell lesions enhance motor seizures but reduce wet dog shakes induced by mu opioid receptor agonist. 216 33

The inducible 72-kDa heat shock protein (HSP72) is a highly conserved stress protein that is expressed in CNS cells and may play a role in protection from neural injury. We used a monoclonal antibody to HSP72 and immunocytochemistry to localize HSP72 in the rat brain 24 h following either 30 or 60 min of flurothyl-induced status epilepticus. Sprague-Dawley rats were anesthetized with halothane, paralyzed, and ventilated, and remained normotensive and well oxygenated for the duration of the seizures. Seizure activity was quantified via analysis of the scalp EEG pattern. HSP72-like immunoreactivity (HSP72-LI) was induced in specific brain regions in a graded fashion that correlated, in part, with the duration and degree of seizure activity. Milder seizures produced HSP72-LI limited to layers 2 and 3 of frontoparietal cortex, dentate hilus cells, and CA3 pyramidal neurons. More extensive seizures led to HSP72-LI in layers 2, 3 and 5 of frontoparietal and visual cortex, dentate hilus cells, CA1 and CA3 pyramidal neurons, and certain thalamic and amygdaloid nuclei. These are similar to many, but not all, of the brain regions known to be injured with this model. No HSP72-LI was observed in sham-treated controls or flurothyl-treated animals whose seizures were controlled with pentobarbital. HSP72-LI thus localizes to certain regions of seizure-induced injury, and may provide a sensitive method of detecting neuronal 'stress' or injury relatively soon after status epilepticus. Whether or not HSP72 synthesis plays a protective role in the pathogenesis of seizures, or is only a marker for cell injury, remains to be determined.
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PMID:The pattern of 72-kDa heat shock protein-like immunoreactivity in the rat brain following flurothyl-induced status epilepticus. 228 19

A study of seizure activity and neuronal cell death produced by intracerebroventricular kainic acid had suggested that seizures conveyed by the hippocampal mossy fibers are more damaging to CA3 pyramidal cells than seizures conveyed by other pathways. To test this idea, the effects of a unilateral mossy fiber lesion were determined on seizure activity and neuronal degeneration provoked by repetitive electrical stimulation of the hippocampal fimbria in unanesthetized rats. Fimbrial stimulation resulted in self-sustained status epilepticus accompanied by neuronal degeneration in several brain regions, including area CA3 of the hippocampal formation. A unilateral mossy fiber lesion more readily attenuated the electrographic and behavioral seizures provoked by fimbrial stimulation than those provoked by kainic acid. If status epilepticus developed in the presence of a mossy fiber lesion, denervated CA3 pyramidal cells were still destroyed, although similar lesions protect these neurons from kainic acid-induced status epilepticus. Thus the two models of status epilepticus employ somewhat different seizure circuitries and neurodegenerative mechanisms. Seizures which involve the mossy fiber projection are not necessarily more damaging to CA3 pyramidal cells than seizures which do not.
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PMID:Stimulation-induced status epilepticus: role of the hippocampal mossy fibers in the seizures and associated neuropathology. 233 10

The time course and severity of the excitotoxic syndrome induced in rats by s.c. injection of 10 mg/kg kainic acid (KA) was modified by pretreatment with MK801, a non-competitive inhibitor of the NMDA receptor, at doses of 0.1, 1 and 10 mg/kg. A dose-dependent increase in the severity of the KA-induced electrographic (EEG) manifestations of epilepsy was seen after MK801. This consisted of an earlier appearance and higher number of EEG seizures, longer time spent in seizures, and an earlier onset of status epilepticus. In contrast, behavioral seizures were increased only in the 0.1 mg/kg MK801 group, but abolished by higher doses. On the contrary, wet dog shakes were progressively reduced with increasing doses of MK801. Four of the 9 animals receiving KA-only group and 3 of the 10 animals in the 1 and 10 mg MK801 groups were sacrificed 5 days after KA. The brain of the KA-only rats presented diffuse gross and microscopic evidence of hemorrhagic necrosis and neuronal damage; the MK801 rats showed only minimal neuronal loss in the CA3 hippocampal sector. This study demonstrates that neuronal damage and epileptiform activity can be dissociated. Furthermore, it confirms the protective effect of MK801 against neuronal damage caused by multiple factors. Lastly, it emphasizes the need for EEG monitoring in order to accurately assess any epileptic/antiepileptic effect.
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PMID:Potentiation of kainic acid epileptogenicity and sparing from neuronal damage by an NMDA receptor antagonist. 254 57

Subconvulsant doses (20 mg/kg) of pilocarpine administered to a kindled rat convert a kindled seizure to status epilepticus. The hippocampus is involved in such status epilepticus. Furthermore, evidence is accumulating that GABA-mediated inhibition in the hippocampus is chronically diminished by kindling. The studies presented here compared the electrophysiologic effects of pilocarpine in vivo in the CA1 region of the hippocampus in naive and amygdala-kindled rats. A paired pulse paradigm previously shown to quantify the potency of GABAergic inhibition was employed. Stimuli were delivered in the CA3 region of urethane-anesthetized rats and population spikes were recorded in the contralateral CA1 region. In naive rats, pilocarpine (6-60 mg/kg) caused a left shift in the input-output curve measuring stimulus intensity vs population spike amplitudes, indicating an increase in neuronal excitability. In addition, paired pulse inhibition was reduced for interpulse intervals less than 70 ms. In amygdala-kindled rats, neuronal excitability was also enhanced following pilocarpine administration. The potency of baseline paired pulse inhibition was decreased in kindled rats compared to naive controls. Following pilocarpine, inhibition for interpulse intervals less than 70 ms was further reduced, but to a lesser extent than in naive rats. These findings suggest that the ability of subconvulsive doses of pilocarpine to change a discrete kindled seizure triggered by one stimulus to status epilepticus depends on the suppression of GABAergic inhibition below a critical level.
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PMID:Reduction of paired pulse inhibition in the CA1 region of the hippocampus by pilocarpine in naive and in amygdala-kindled rats. 272 29

Kainic acid (KA, 8-15 ng) was injected into the amygdala of conscious freely moving rats via chronically implanted fused silica cannulas. At 15-25 min after the injection, most rats suffered a limbic seizure attack of short duration, consisting of mastication, forelimb clonus, and raising on hind limbs, behaviorally indistinguishable from kindled seizures. Typically, the attack was followed by stereotypies, intense exploration, and by 1 or 2 more attacks. About 60 min after the injection, most rats appeared normal again and histopathological changes in their brains did not exceed those seen in vehicle-injected rats. In 3 cases, however, recurrent seizures culminated in behavioral status epilepticus 60-90 min after the injection. The status epilepticus was stopped by i.p. injection of diazepam (10 mg/kg) after a duration of 10 min (1 case) and 30 min (2 cases), respectively. After 10 min status epilepticus, we observed marginal neuronal damage with slight gliosis in both hippocampi (CA3 and CA1); after 30 min, hippocampal histopathology was more pronounced, with additional necrosis of the ipsilateral piriform cortex. After 0.8 microgram KA, a hundredfold higher dose, the incidence of limbic seizures during the first 40 min was not significantly higher (9/12) than after the lower KA doses (13/19). However, a significantly higher proportion of rats exhibited long-lasting seizure activity, associated with confluent destruction of CA3 pyramidal cells and additional seizure-related brain damage. Our results show that limbic motor seizures do not inevitably lead to histopathological changes in the brain, provided they do not culminate in a state of permanent seizure activity.
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PMID:Limbic seizures without brain damage after injection of low doses of kainic acid into the amygdala of freely moving rats. 274 56

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


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