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

The pattern of hippocampal cell death has been studied following hippocampal seizure activity and status epilepticus induced by 110-min stimulation of the perforant pathway in awake rats. The order of vulnerability of principal cells in the different hippocampal subfields--as determined by silver impregnation--was found to be very similar to the pattern found in ischemia; i.e., dentate hilus greater than CA1, subiculum greater than CA3c greater than CA3a,b greater than dentate granule cells. The hilar somatostatin-containing cells were the most vulnerable cell type, whereas all other subpopulations of nonprincipal neurons--visualized by immunocytochemistry for the calcium binding proteins parvalbumin and calbindin--were remarkably resistant. Pyramidal cells in the CA3 region containing neither of the examined calcium binding proteins were more resistant to overexcitation than CA1 pyramidal cells, most of which do contain calbindin. This indicates that no simple relationship exists between vulnerability in status epilepticus and neuronal calcium binding protein content, and that local and/or systemic hypoxia during status epilepticus may be responsible for the ischemic pattern of cell death.
 ...
PMID:Pattern of neuronal death in the rat hippocampus after status epilepticus. Relationship to calcium binding protein content and ischemic vulnerability. 134 49

A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation.
 ...
PMID:Mechanisms in the development of limbic status epilepticus and hippocampal neuron loss: an experimental study in a model of status epilepticus induced by kindling-like electrical stimulation of the deep prepyriform cortex in rats. 153 85

Immunocytochemistry with specific antisera was used to assess regional levels of six immediate early gene encoded proteins (KROX-24, c-FOS, FOS B, c-JUN, JUN B and JUN D) in the rat hippocampus after 15 min of bicuculline-induced seizures. Serial sections of the dorsal hippocampus were examined at various postictal recovery periods up to 24 h. The results demonstrate a complex temporal and spatial pattern of immediate early gene synthesis and accumulation. Three major categories of immediate early gene products could best be distinguished in the dentate gyrus: KROX-24 and c-FOS showed a concurrent rapid rise with peak levels at 2 h and a return to baseline levels within 8 h after seizure termination. FOS B, c-JUN and JUN B levels increased more gradually with peak intensities in the dentate gyrus reached at 4 h. These immediate early gene products showed above normal levels in various hippocampal subpopulations up to 24 h. JUN D exhibited the most delayed onset combined with a prolonged increase of seizure-induced immunoreactivity. Irrespective of this differential temporal expression profile of individual transcription factors, the sequence of induction in the hippocampal subpopulations was identical for all immediate early gene-encoded proteins examined: first in the dentate gyrus granule cells followed by CA1 and CA3 neurons, respectively. Our data indicate an asynchronous synthesis of several immediate early gene-encoded proteins in the brain after status epilepticus. FOS and JUN proteins act via homo- or heterodimer complexes at the AP-1 and other DNA binding sites. The different time-courses for individual immediate early gene products strongly suggest, that at different time-points after status epilepticus, different AP-1 complexes are effective. In vitro studies have shown that different AP-1 complexes possess different DNA binding affinities as well as different transcriptional regulatory effects. Our results suggest that these molecular mechanisms are also effective in vivo.
 ...
PMID:Induction of immediate early gene encoded proteins in the rat hippocampus after bicuculline-induced seizures: differential expression of KROX-24, FOS and JUN proteins. 160 23

The relationship between an episode of status epilepticus, the resulting hippocampal pathology, and the subsequent development of pathophysiological changes possibly relevant to human epilepsy was explored using the experimental epilepsy model of perforant path stimulation in the rat. Granule cell hyperexcitability and decreased feedforward and feedback inhibition were evident immediately after 24 hours of intermittent perforant path stimulation and persisted relatively unchanged for more than 1 year. All of the pathophysiological changes induced by perforant path stimulation were replicated in normal animals by a subconvulsive dose of bicuculline, suggesting that the permanent "epileptiform" abnormalities produced by sustained perforant path stimulation may be due to decreased GABA-mediated inhibition. Granule cell pathophysiology was seen only in animals that exhibited a loss of adjacent dentate hilar mossy cells and hilar somatostatin/neuropeptide Y-immunoreactive neurons. GABA-immunoreactive dentate basket cells survived despite the extensive loss of adjacent hilar neurons. However, parvalbumin immunoreactivity, present normally in a subpopulation of GABA-immunoreactive dentate basket cells, was absent on the stimulated side. Whether this represents decreased parvalbumin synthesis in surviving basket cells or a loss of a specific subset of inhibitory cells is unclear. Hyperexcitability and decreased paired-pulse inhibition in response to ipsilateral perforant path stimulation were also present in the CA1 pyramidal cell layer on the previously stimulated side, despite minimal damage to CA1 pyramidal cells or interneurons. The possibility that CA1 inhibitory neurons were hypofunctional or "dormant" due to a loss of excitatory input to inhibitory cells from damaged CA3 pyramidal cells was tested by stimulating the contralateral perforant path in order to activate the same CA1 basket cells via different inputs. Contralateral stimulation evoked CA1 pyramidal cell paired-pulse inhibition immediately in the previously stimulated hippocampus. Thus, we propose the "dormant basket cell" hypothesis, which implies that despite malfunction, inhibitory systems remain intact in "epileptic" tissue and are capable of functioning if appropriately activated.
 ...
PMID:Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the "dormant basket cell" hypothesis and its possible relevance to temporal lobe epilepsy. 168 84

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.
 ...
PMID:Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus. 171 86

A pilot case-control quantitative study of the hippocampus in patients with severe status epilepticus was performed to identify specific patterns of pyramidal cell loss. Pyramidal cell densities from five patients who died following status epilepticus were compared with five normal controls and five controls matched for age, hypoxia/ischemia, previous epilepsy, and alcohol abuse. Neuronal densities were greatest in the normal control group and least in patients with status epilepticus. Significant reductions were identified in Sommer's sector (prosubiculum and CA1) as well as in CA3 when compared to normal controls.
 ...
PMID:Hippocampal pyramidal cell loss in human status epilepticus. 173 57

In order to study spatial interactions during low magnesium induced epileptiform activity, changes in extracellular potassium concentration ([K+]0) and associated slow field potentials (f.p.'s) were recorded in thin rat temporal cortex slices (400 microns) containing the neocortical temporal area 3 (Te3), the entorhinal cortex (EC) and the hippocampal formation with the dentate gyrus, area CA3 and CA1 and the subiculum (Sub). The epileptiform activity was characterized by short recurrent epileptiform discharges (40 to 80 ms, 20/min) in areas CA3 and CA1 and by interictal discharges and tonic and clonic seizure like events (SLE's) (13-88s) in the EC, Te3 and Sub. While interictal discharges occurred independent of each other in the different subfields, the three areas became synchronized during the course of a SLE. The EC, Te3 and Sub all could represent the "focus" for generation of the SLE's. This initiation site for SLE's sometimes changed from one area to another. The characteristics of the rises in [K+]0 and subsequent undershoots were comparable to previous observations in in vivo preparations. Interestingly, rises in [K+]0 could start before actual onset of seizure like activity in secondarily recruited areas. The epileptiform activity could change its characteristics to either a state of recurrent tonic discharge episodes or to a continuous clonic discharge state reminiscent of various forms of status epilepticus. We did not observe, in any of these states, active participation by area CA3 in the epileptiform activity of the EC in spite of clear projected activity to the dentate gyrus. Even after application of picrotoxin (20 microM), area CA3 did not actively participate in the SLE's generated in the entorhinal cortex. When baclofen (2 microM) was added to the picrotoxin containing medium, SLE's occurred both in the entorhinal cortex and in area CA3, suggesting that inhibition of inhibitory interneurons by baclofen could overcome the "filtering" of projected activity from the entorhinal cortex to the hippocampus.
 ...
PMID:Regional and time dependent variations of low Mg2+ induced epileptiform activity in rat temporal cortex slices. 178 28

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.
 ...
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.
 ...
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)
 ...
PMID:Ventral hippocampal dentate granule cell lesions enhance motor seizures but reduce wet dog shakes induced by mu opioid receptor agonist. 216 33


1 2 3 4 5 6 7 8 9 10 Next >>