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)

Status epilepticus in the immature brain induces neuronal injury in the hippocampal formation, but the mode and mechanism of death are poorly understood. Our laboratory has recently investigated the role of caspase-3, -8, and -9 in neuronal injury, using a lithium-pilocarpine model of status epilepticus in 2-week-old rat pups. Our results showed that dying neurons in the dentate gyrus and CA1-subiculum area do not share the same mechanism of death. In CA1-subiculum, caspase-8 upregulation preceded caspase-3 activation in morphologically necrotic neurons. The pan-caspase inhibitor Q-VD-OPH reduced CA1 damage, showing that caspases contribute to status epilepticus-induced necrosis. In the dentate gyrus, dying neurons were caspase-9 and -3 immunoreactive and morphologically apoptotic. It is not clear why the same seizures cause different types of cell death in neurons that are connected in series along the same hippocampal circuit, but the apoptotic dentate neurons express doublecortin, and do not express calbindin-D28k, suggesting that their immaturity may be a factor in producing an apoptotic mode of death.
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PMID:Distinct caspase pathways mediate necrosis and apoptosis in subpopulations of hippocampal neurons after status epilepticus. 2061 2

The transient receptor potential vanilloid-1 (TRPV1) receptor has been implicated in the development of epileptic seizures. We examined the effect of the TRPV1 agonist capsaicin on epileptic seizures, neuronal injury and oxidative stress in a model of status epilepticus induced in the rat by intraperitoneal (i.p.) injections of pentylenetetrazole (PTZ). Capsaicin was i.p. given at 1 or 2 mg/kg, 30 min before the first PTZ injection. Other groups were i.p. treated with the vehicle or the anti-epileptic drug phenytoin (30 mg/kg) alone or co-administered with capsaicin at 2 mg/kg. Brain levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, and paraoxonase-1 (PON-1) activity, seizure scores, latency time and PTZ dose required to reach status epilepticus were determined. Histopathological assessment of neuronal damage was done. Results showed that brain MDA decreased by treatment with capsaicin, phenytoin or capsaicin/phenytoin. Nitric oxide decreased by capsaicin or capsaicin/phenytoin. GSH and PON-1 activity increased after capsaicin, phenytoin or capsaicin/phenytoin. Mean total seizure score decreased by 48.8% and 66.3% by capsaicin compared with 78.7% for phenytoin and 69.8% for capsaicin/phenytoin treatment. Only phenytoin increased the latency (115.7%) and threshold dose of PTZ (78.3%). Capsaicin did not decrease the anti-convulsive effect of phenytoin but prevented the phenytoin-induced increase in latency time and threshold dose. Neuronal damage decreased by phenytoin or capsaicin at 2 mg/kg but almost completely prevented by capsaicin/phenytoin. Thus in this model of status epilepticus, capsaicin decreased brain oxidative stress, the severity of seizures and neuronal injury and its co-administration with phenytoin afforded neuronal protection.
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PMID:Capsaicin Exerts Anti-convulsant and Neuroprotective Effects in Pentylenetetrazole-Induced Seizures. 3210 Jan 66