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 electrophysiological effects of the high-fat, low-carbohydrate ketogenic diet (KD) were assessed in normal and epileptic [kainic-acid(KA)-treated] adult rats using hippocampal slices. In the first set of experiments, normal rats were fed the KD or a standard control diet for 6-8 weeks (beginning on postnatal day 56, P56), after which they were sacrificed for hippocampal slices. All rats on the KD became ketotic. The baseline effects of the KD were determined by comparing extracellular measures of synaptic transmission and responses to evoked stimulation, and hippocampal excitability was tested in Mg(2+)-free medium. There were no differences in EPSP slope, input/output relationship, responses to evoked stimulation or Mg(2+)-free burst frequency between slices from control and KD-fed rats. In another set of experiments, rats were made epileptic by intraperitoneal injection of kainic acid (KA) on P54, which caused status epilepticus followed by the development of spontaneous recurrent seizures (SRS) over the next few weeks. Two days after KA-induced status, rats were divided into a control-fed group and a KD-fed group. Animals on the KD had significantly fewer SRS over the ensuing 8 weeks. In hippocampal slices from KA-treated, KD-fed rats, there were fewer evoked CA1 population spikes than from slices of control-fed rats. These results suggest that the KD does not alter baseline electrophysiological parameters in normal rats. In rats made chronically epileptic by administration of KA, KD treatment was associated with fewer spontaneous seizures and reduced CA1 excitability in vitro. Therefore, at least part of the KD mechanism of action may involve long-term changes in network excitability.
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PMID:Electrophysiological observations in hippocampal slices from rats treated with the ketogenic diet. 1057 63

Dysregulated adult hippocampal neurogenesis occurs in many temporal lobe epilepsy (TLE) models. Most dentate granule cells (DGCs) generated in response to an epileptic insult develop features that promote increased excitability, including ectopic location, persistent hilar basal dendrites (HBDs), and mossy fiber sprouting. However, some appear to integrate normally and even exhibit reduced excitability compared to other DGCs. To examine the relationship between DGC birthdate, morphology, and network integration in a model of TLE, we retrovirally birthdated either early-born [EB; postnatal day (P)7] or adult-born (AB; P60) DGCs. Male rats underwent pilocarpine-induced status epilepticus (SE) or sham treatment at P56. Three to six months after SE or sham treatment, we used whole-cell patch-clamp and fluorescence microscopy to record spontaneous excitatory and inhibitory currents from birthdated DGCs. We found that both AB and EB populations of DGCs recorded from epileptic rats received increased excitatory input compared with age-matched controls. Interestingly, when AB populations were separated into normally integrated (normotopic) and aberrant (ectopic or HBD-containing) subpopulations, only the aberrant populations exhibited a relative increase in excitatory input (amplitude, frequency, and charge transfer). The ratio of excitatory-to-inhibitory input was most dramatically upregulated for ectopically localized DGCs. These data provide definitive physiological evidence that aberrant integration of post-SE, AB DGCs contributes to increased synaptic drive and support the idea that ectopic DGCs serve as putative hub cells to promote seizures.SIGNIFICANCE STATEMENT Adult dentate granule cell (DGC) neurogenesis is altered in rodent models of temporal lobe epilepsy (TLE). Some of the new neurons show abnormal morphology and integration, but whether adult-generated DGCs contribute to the development of epilepsy is controversial. We examined the synaptic inputs of age-defined populations of DGCs using electrophysiological recordings and fluorescent retroviral reporter birthdating. DGCs generated neonatally were compared with those generated in adulthood, and adult-born (AB) neurons with normal versus aberrant morphology or integration were examined. We found that AB, ectopically located DGCs exhibit the most pro-excitatory physiological changes, implicating this population in seizure generation or progression.
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PMID:Altered Synaptic Drive onto Birthdated Dentate Granule Cells in Experimental Temporal Lobe Epilepsy. 3127 Jan 58