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)

In the aftermath of prolonged continuous seizure activity (status epilepticus, SE), neuronal cell death occurs in the brain regions through which the seizure propagates. Recent studies have implicated apoptotic processes in this seizure-related injury. Because activation of caspase-3-like cysteine proteases plays a crucial role in mammalian neuronal apoptosis, we explored the possibility that activation of caspase-3 is involved in the neuronal apoptotic cell death that occurs in rat brain following SE induced by systemic kainic acid. Caspase-3 activity was determined immunocytochemically using CM1 antibodies specific for catalytically active subunit (p17) of the enzyme. We found an induction of caspase-3 activity in rhinal cortex and amygdala at 24 h after SE. To determine whether activation of caspase-3-like proteases is a necessary component of the injury process, we delivered a caspase-3 inhibitor, z-DEVD-fmk, into the lateral ventricle prior to, and following SE. z-DEVD-fmk treatment substantially attenuated apoptotic cell death after SE, both in hippocampus and rhinal cortex, as evaluated by analysis of internucleosomal DNA fragmentation and neuronal nuclear morphology. Our findings implicate caspase-3 cysteine protease in the neurodegenerative response to SE and suggest that this degeneration can be attenuated by inhibition of caspase-3-like enzyme activity.
 ...
PMID:Intracerebral injection of caspase-3 inhibitor prevents neuronal apoptosis after kainic acid-evoked status epilepticus. 1068 42

Cystatin C (CSTC), a cysteine protease inhibitor, has been implicated in the processes of neuronal degeneration and repair of the nervous system. Using serial analysis of gene expression (SAGE), we recently identified CSTC as one of the genes that are overexpressed after electrically induced status epilepticus (SE). In the present study, Western blot analysis extended the SAGE results, showing increased CSTC protein in the hippocampus and entorhinal cortex. Immunocytochemistry revealed an increase in CSTC expression in glial cells, which was first apparent 24 h after onset of SE, and persisted for at least 3 months. Double immunolabelling confirmed that both reactive astrocytes, and activated microglia were CSTC immunopositive. Within the hippocampus, up-regulation was also observed in neuronal cells within one day after SE. Up-regulation was still present in hippocampal pyramidal cells and surviving interneurons of chronic epileptic rats (3-8 months post-SE). This study demonstrates that status epilepticus leads to a widespread and persistent up-regulation of CSTC in the hippocampus and entorhinal cortex, which may represent an intrinsic neuroprotective mechanism in the course of epileptogenesis that may counteract progression of the disease.
 ...
PMID:Cystatin C, a cysteine protease inhibitor, is persistently up-regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy. 1172 10

Stroke is a major cause of epilepsy, but the molecular mechanisms underlying post-stroke epileptogenesis are unknown. The expression of cystatin C, a cysteine protease inhibitor, is increased in the hippocampus during status epilepticus (SE)-induced epileptogenesis, and regulates both cell death and birth. To test the hypothesis that increased cystatin C expression represents a common molecular alteration induced by epileptogenic brain insults, we investigated the time course, cellular localization, and association of cystatin C expression with neuronal damage during post-stroke epileptogenesis. Stroke was induced with photothrombosis, which leads to epilepsy in approximately 20-30% of rats. Cystatin C expression was increased in the CA1 area of the hippocampus 4 days after photothrombosis, when the diameter of the lesion was the largest. Double-labeling and confocal analysis indicated that cystatin C was expressed in astrocytes and microglia. Unlike after SE, cystatin C expression did not change in the dentate gyrus. Also, increased cystatin C expression was not associated with neurodegeneration, which was demonstrated as an absence of Fluoro Jade B-positive cells in adjacent sections. The present study provides evidence that cystatin C may be involved in cellular alterations that occur after an epileptogenic insult, not only after SE but also after photothrombotic stroke.
 ...
PMID:Cystatin C expression is increased in the hippocampus following photothrombotic stroke in rat. 1630 30