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 molecular regulation of seizure-induced neuronal death may involve interactions between proteins of the Bcl-2 and 14-3-3 families. To further examine these pathways we performed subcellular fractionation on hippocampi obtained following a brief period of status epilepticus in the rat. Western blotting determined seizures induced caspase-8 cleavage and increased Bcl-w levels within the cytoplasm. Bax, Bad and Bid were largely present within the cytoplasm before and after seizures, although some Bax and, following seizures, truncated Bid was detected in mitochondria. Levels of 14-3-3 were significantly reduced in the cytoplasm and microsomal fractions. These data establish the expression and distribution profile of key Bcl-2 family proteins and the signaling chaperone 14-3-3 in the rat and provide additional evidence for the activation of programmed cell death pathways by seizures.
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PMID:Subcellular distribution of Bcl-2 family proteins and 14-3-3 within the hippocampus during seizure-induced neuronal death in the rat. 1503 20

Activation of the caspase-dependent cell death pathways has been shown in focal seizures, but whether this occurs in prolonged generalized seizures is not known. We investigated whether the initiator caspase in the extrinsic pathway, caspase-8, or the intrinsic pathway, caspase-9, is activated during the first 24 h following lithium-pilocarpine-induced status epilepticus, when neuronal death is maximal and widespread. The thymuses of rats given methamphetamine were used as positive controls for caspase-3-activated cellular apoptosis. Following methamphetamine treatment, caspase-9 but not caspase-8 was activated in thymocytes. However, 6 or 24 h following status epilepticus, none of 26 brain regions studied showed either caspase-8 or -9 activation by immunohistochemistry, western blotting and enzyme activity assays. Our results provide evidence against the activation of the extrinsic and intrinsic caspase pathways in generalized seizures, which produce morphologically necrotic neurons with internucleosomal DNA cleavage (DNA laddering), a programmed process. In contrast, there is increasing evidence that caspase-independent programmed mechanisms play a prominent role in seizure-induced neuronal death.
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PMID:Caspase-dependent programmed cell death pathways are not activated in generalized seizure-induced neuronal death. 1720 52

The mechanism of status epilepticus-induced neuronal death in the immature brain is not fully understood. In the present study, we examined the contribution of caspases in our lithium-pilocarpine model of status epilepticus in 14 days old rat pups. In CA1, upregulation of caspase-8, but not caspase-9, preceded caspase-3 activation in morphologically necrotic cells. Pretreatment with a pan-caspase inhibitor provided neuroprotection, showing that caspase activation was not an epiphenomenon but contributed to neuronal necrosis. By contrast, upregulation of active caspase-9 and caspase-3, but not caspase-8, was detected in apoptotic dentate gyrus neurons, which were immunoreactive for doublecortin and calbindin-negative, two features of immature neurons. These results suggest that, in cells which are aligned in series as parts of the same excitatory hippocampal circuit, the same seizures induce neuronal death through different mechanisms. The regional level of neuronal maturity may be a determining factor in the execution of a specific death program.
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PMID:Vulnerability of postnatal hippocampal neurons to seizures varies regionally with their maturational stage. 1987 60

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