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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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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

Somatostatin-, neuropeptide Y-, neurokinin B- and cholecystokinin-containing neurons were investigated in the rat hippocampus in two chronic models of temporal lobe epilepsy, i.e. 30 days after rapid kindling or electrically induced status epilepticus (post-status epilepticus). After rapid kindling, somatostatin immunoreactivity was strongly increased in interneurons and in the outer and middle molecular layer of the dentate gyrus. In four of six post-status epilepticus rats (status epilepticus I rats), somatostatin immunoreactivity was slightly increased in the dorsal but decreased in the ventral dentate gyrus and molecular layer. Somatostatin immunoreactivity decreased in neurons of the dorsal hilus in the two other post-status epilepticus rats investigated, while a complete loss was found in the respective ventral extension (status epilepticus-II rats). These changes were associated with a different extent of neurodegeneration as assessed by Nissl staining. Similarly, neuropeptide Y immunoreactivity was enhanced in neurons of the hilus and in the middle and outer molecular layer of the dentate gyrus in the dorsal hippocampus of rapidly kindled and status epilepticus-I rats. Neuropeptide Y and neurokinin B immunoreactivity was enhanced in the mossy fibers of all post-status epilepticus rats, but not in the rapidly kindled rats. In status epilepticus-II rats, neuropeptide Y-and neurokinin B-positive fibers were also detected in the infrapyramidal region of the stratum oriens of CA3 and in the inner molecular layer of the dentate gyrus in the dorsal and ventral hippocampus respectively, labeling presumably sprouted mossy fibers. Increased staining of neuropeptide Y and neurokinin B was found in the alveus after rapid kindling. Cholecystokinin immunoreactivity was markedly increased in the cerebral cortex, Ammon's horn and the molecular layer of the dentate gyrus in the ventral hippocampus of rapidly kindled and post-status epilepticus rats. The lasting changes in the immunoreactive pattern of various peptides in the hippocampus may reflect functional modifications in the corresponding peptide-containing neurons. These changes may be involved in chronic epileptogenesis, which evolves in response to limbic seizures.
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PMID:Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy. 859 52

The in vitro release of somatostatin and neuropeptide Y, their tissue concentration and immunocytochemical pattern were examined in the entorhinal cortex of chronically epileptic rats. A systemic administration of 12 mg/kg kainic acid causing generalized tonic-clonic seizures for at least 3 h after injection was used to induce, 60 days later, a chronically enhanced susceptibility to seizures in the rats. The release of both peptides under depolarizing conditions was significantly reduced by 15% on average from slices of the entorhinal cortex two days after kainic acid-induced status epilepticus. At 60 days, the spontaneous and 30 mM KCl-induced release of somatostatin was significantly enhanced by 30% on average. The release induced by 100 mM KCl was raised by 70%. The spontaneous, 30 mM and 100 mM KCl-induced release of neuropeptide Y from the same slices was increased, respectively, by 120%, 76% and 36%. The late changes were associated with an increased tissue concentration of neuropeptide Y but not of somatostatin. This was confirmed by immunocytochemical evidence showing that neuropeptide Y-, but not somatostatin-immunoreactive neurons were increased in the entorhinal cortex of kainic acid-treated rats. These results indicate that neurotransmission mediated by somatostatin and neuropeptide Y, two peptides previously shown to play a role in limbic epileptogenesis, is enhanced in the entorhinal cortex of chronically epileptic rats.
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PMID:Functional activation of somatostatin- and neuropeptide Y-containing neurons in the entorhinal cortex of chronically epileptic rats. 893 Oct 18

Using immunocytochemistry and in situ hybridization analysis of mRNA, we investigated the changes in the expression of somatostatin and neuropeptide Y (NPY) in the rat hippocampal principal neurons in kindling or after electrically induced status epilepticus (SE), two models of limbic epilepsy associated with different chronic sequelae of seizures and seizure-related neuropathology. At the preconvulsive stage 2 of kindling and after three consecutive tonic-clonic seizures (stage 5) but not after a single-discharge (AD), somatostatin and NPY immunoreactivity (IR) were markedly increased in interneurons of the deep hilus and the polymorphic cell layer and their presumed projections to the outer molecular layer of the dentate gyrus. Increased mRNA levels were observed in the same neurons. NPY IR and mRNA were highly expressed in pyramidal-shaped basket cells at both stages of kindling. IR was similar two days after stages 2 or 5 of kindling while less pronounced effects were observed one week after kindling completion. Peptide-containing neurons in the hilus appeared well preserved in spite of an average of 24% reduction of Nissl stained cells (p < 0.01) in the stimulated and contralateral hippocampus at stage 5. No sprouting of mossy fibres in the inner molecular layer was found as assessed by Timm staining. Thirty days after SE, somatostatin IR was slightly reduced or similar to controls in the ventral dentate gyrus and molecular layer in four or six rats (SE-I group) while in the two other post-SE rats (SE-II), somatostatin IR was lost. These changes were associated with a different extent of neurodegeneration as assessed by cell counting of Nissl stained sections. In the granule cells/mossy fibres NPY-IR was transiently expressed at stage 2 and after a single AD. Differently, NPY-IR was persistently enhanced in the mossy fibres of all post-SE rats particularly in the SE-II group. In these rats, NPY immunoreactive fibres were detected in the infrapyramidal region of the stratum oriens CA3 and in the inner molecular layer of the dentate gyrus very likely labeling sprouted mossy fibres. In the hippocampus proper of kindled rats, somatostatin and NPY IR were respectively enhanced in the stratum lacunosum moleculare, the subiculum and in the alveus while no significant changes were observed after SE. Changes in peptide expression were bilateral and involved both the dorsal and the ventral hippocampus. The lasting modifications in peptides IR and mRNA expression in distinct neuronal populations of the hippocampus may reflect functional modifications neurons and play a role in limbic epileptogenesis.
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PMID:Functional changes in somatostatin and neuropeptide Y containing neurons in the rat hippocampus in chronic models of limbic seizures. 898 6

We re-examined the proposed resistance of the immature brain to seizure-induced damage. In awake, freely moving rat pups, intermittent perforant path stimulation produced selective hippocampal cell loss and reduction in paired-pulse inhibition. During 16 h of stimulation, animals showed frequent wet dog shakes and hind-limb scratching movements but no convulsive motor activity. In situ end-labelling performed 2 h after the end of stimulation showed an intense band of positively-labelled eosinophilic cells with condensed profiles bilaterally in the dentate granule cell layer of stimulated animals. Control animals showed no in situ end-labelling positivity in the dentate gyrus. These cells were not observed 24 h later, suggestive of rapidly scavenged apoptotic cells. One day after the end of stimulation, many necrotic interneurons with eosinophilic cytoplasm and pyknotic nuclei were observed in the hilus of the stimulated dentate gyrus in all rats tested. Hippocampal pyramidal cells in CA1, CA3 and subiculum showed bilateral damage greater on the side of stimulation, and prepiriform cortex sustained bilateral symmetrical lesions. One month after perforant path stimulation, Cresyl Violet staining showed the number of large hilar interneurons (>15 microm) was reduced on the stimulated side (54.1 +/- 12.2) compared to the non-stimulated side (100.5 +/- 10.2 cells, P<0.01). Immunohistochemical analysis showed significant losses in somatostatin (8.5 +/- 1.6 stimulated side, 22.8 +/- 3.8 unstimulated side, P<0.05) and neuropeptide Y (12.8 +/- 3.2 stimulated side, 17.0 +/- 4.1 unstimulated side, P<0.05) immunoreactive cells in the stimulated hilus but no loss of parvalbumin-immunoreactive cells. Significant reductions in paired-pulse inhibition were found after stimulation but there was some return of inhibition by one month. These combined data demonstrate that the immature brain can incur damage as a result of prolonged seizure-like hippocampal activity mimicking status epilepticus in immature rats. The hippocampal damage produced by perforant path stimulation is associated with the immediate loss of physiological inhibition suggesting important modification of excitatory control in an extremely epileptogenic region of the brain.
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PMID:Hippocampal stimulation produces neuronal death in the immature brain. 946 46

There has been direct evidence of gamma-aminobutyric acidA receptor modification during status epilepticus. Neuropeptides galanin and neuropeptide Y were demonstrated to play a role in terminating status epilepticus. Many of the CA3 pyramidal neurons destined to die as a consequence of status epilepticus were demonstrated to diminish expression of the GluR2 subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors. It was demonstrated that the pattern of cell loss due to status epilepticus is distinct in immature pups compared with adult rats. The genetic basis for susceptibility to neuronal loss during status epilepticus was described. There was increasing evidence of unique receptors and ion channels in the epileptic brain. The molecular studies of epileptic gamma-aminobutyric acidA receptors present on dentate granule cells of rats with temporal lobe epilepsy revealed altered gene and receptor expression before onset of recurrent spontaneous seizures. They also revealed insertion of new gamma-aminobutyric acidA receptors in the inhibitory synapses present on soma and proximal dendrites of dentate granule cells.
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PMID:Status epilepticus in epileptogenesis. 1022 52

Brain derived neurotrophic factor (BDNF) has been suggested to be involved in epileptogenesis. Both pro- and antiepileptogenic effects have been reported, but the exact physiological role is still unclear. Here, we investigated the role of endogenous BDNF in epileptogenesis by using transgenic mice overexpressing truncated trkB, a dominant negative receptor of BDNF. After induction of status epilepticus (SE) by kainic acid, the development of spontaneous seizures was monitored by video-EEG system. Hilar cell loss, and the number of neuropeptide Y immunoreactive cells were studied as markers of cellular damage, and mossy fibre sprouting was investigated as a plasticity marker. Our results show that transgenic mice had significantly less frequent interictal spiking than wild-type mice, and the frequency of spontaneous seizures was lower. Furthermore, compared to wild-type animals, transgenic mice had less severe seizures with later onset and mortality was lower. In contrast, no differences between genotypes were observed in any of the cellular or plasticity markers. Our results suggest that transgenic mice with decreased BDNF signalling have reduced epileptogenesis.
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PMID:Decreased BDNF signalling in transgenic mice reduces epileptogenesis. 1188 52

Although it is now established that neurogenesis of dentate gyrus granule cells increases after experimental seizures, little is currently known about the function of the new granule cells. One question is whether they become integrated into the network around them. Recent experiments that focused on the newly born granule cells in the hilus showed that indeed the new cells appear to become synchronized with host hippocampal neurons [Scharfman et al. (2000) J. Neurosci. 20, 6144-6158]. To address this issue further, we asked whether the new hilar granule cells were active during spontaneous limbic seizures that follow status epilepticus induced by pilocarpine injection. Thus, we perfused rats after spontaneous seizures and stained sections using antibodies to c-fos, a marker of neural activity, and calbindin, a marker of the newly born hilar granule cells [Scharfman et al. (2000) J. Neurosci. 20, 6144-6158]. We asked whether calbindin-immunoreactive hilar neurons were also c-fos-immunoreactive.C-fos was highly expressed in calbindin-immunoreactive hilar neurons. Approximately 23% of hilar cells that expressed c-fos were double-labeled for calbindin. In addition, other types of hilar neurons, i.e. those expressing parvalbumin or neuropeptide Y, also expressed c-fos. Yet other hippocampal neurons, including granule cells and pyramidal cells, had weak expression of c-fos at the latency after the seizure that hilar neuron expression occurred. In controls, there was very little c-fos or calbindin expression in the hilus.These results indicate that calbindin-immunoreactive hilar cells are activated by spontaneous seizures. Based on the evidence that many of these cells are likely to be newly born, the data indicate that new cells can become functionally integrated into limbic circuits involved in recurrent seizure generation. Furthermore, they appear to do so in a manner similar to many neighboring hilar neurons, apparently assimilating into the local environment. Finally, the results show that a number of hilar cell types are activated during chronic recurrent seizures in the pilocarpine model, a surprising result given that many hilar neurons are thought to be damaged soon after pilocarpine-induced status epilepticus.
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PMID:Spontaneous recurrent seizures after pilocarpine-induced status epilepticus activate calbindin-immunoreactive hilar cells of the rat dentate gyrus. 1195 13

We compared the anticonvulsant actions of dynorphin A (1-13), galanin, neuropeptide Y and somatostatin in a model of self-sustaining status epilepticus (SSSE). SSSE was induced in adult Wistar rats by 30 min intermittent perforant path stimulation. Peptides or saline were injected into the hilus of the dentate gyrus 10 min after the end of perforant path stimulation. EEG was analyzed using Harmonie software (Stellate systems). While all neuropeptides showed significant seizure protecting effects, their anticonvulsant profiles followed different patterns: somatostatin and NPY induced strong, but transient suppression of spikes and seizures, while seizure suppression by dynorphin and galanin was more profound and irreversible.
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PMID:Anticonvulsant effects of four neuropeptides in the rat hippocampus during self-sustaining status epilepticus. 1236 56

The rat dentate gyrus is usually described as relatively homogeneous. Here, we present anatomic and physiological data which demonstrate that there are striking differences between the supra- and infrapyramidal blades after status epilepticus and recurrent seizures. These differences appear to be an accentuation of a subtle asymmetry present in normal rats. In both pilocarpine and kainic acid models, there was greater mossy fiber sprouting in the infrapyramidal blade. This occurred primarily in the middle third of the hippocampus. Asymmetric sprouting was evident both with Timm stain as well as antisera to brain-derived neurotrophic factor (BDNF) or neuropeptide Y (NPY). In addition, surviving NPY-immunoreactive hilar neurons were distributed preferentially in the suprapyramidal region of the hilus. Extracellular recordings from infrapyramidal sites in hippocampal slices of pilocarpine-treated rats showed larger population spikes and weaker paired-pulse inhibition in response to perforant path stimulation relative to suprapyramidal recordings. A single stimulus could evoke burst discharges in infrapyramidal granule cells but not suprapyramidal blade neurons. BDNF exposure led to spontaneous epileptiform discharges that were larger in amplitude and longer lasting in the infrapyramidal blade. Stimulation of the infrapyramidal molecular layer evoked larger responses in area CA3 than suprapyramidal stimulation. In slices from the temporal pole, in which anatomic evidence of asymmetry waned, there was little evidence of physiological asymmetry either. Of interest, some normal rats also showed signs of greater evoked responses in the infrapyramidal blade, and this could be detected with both microelectrode recording and optical imaging techniques. Although there were no signs of hyperexcitability in normal rats, the data suggest that there is some asymmetry in the normal dentate gyrus and this asymmetry is enhanced by seizures. Taken together, the results suggest that supra- and infrapyramidal blades of the dentate gyrus could have different circuit functions and that the infrapyramidal blade may play a greater role in activating the hippocampus.
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PMID:Structural and functional asymmetry in the normal and epileptic rat dentate gyrus. 1245 7


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