title: Expression and activation of caspase 3 following status epilepticus in the rat.
abstract: It is in dispute whether caspase 3 contributes to status epilepticus (SE)-induced cell loss. We hypothesized that caspase 3-mediated cell death continues beyond the acute phase of SE. We induced SE with either kainic acid or electrical stimulation of the amygdala in Wistar and Sprague-Dawley rats. Caspase 3 immunohistochemistry, Western blot analysis and enzyme activity measurements were used to determine cellular localization and the time course of caspase 3 expression and activation. Immunohistochemistry indicated that caspase 3 protein expression increased following SE, peaking at 16-24 h. Cleavage of procaspase 3 to active fragments (p20-17) was detected 2-7 days after SE. Caspase 3 enzyme activity was elevated at 8 h and further increased up to 19.4-fold at 7 days following SE. Activation of caspase 3 after SE occurred in the hippocampus and the extrahippocampal temporal lobe but not in the thalamus. Caspase 3-immunoreactive cells represented only a minority of degenerating cells as assessed by Fluoro-Jade B and TUNEL staining. Analysis of double-labelled sections indicated that active caspase 3 was located in astrocytes rather than neurons or microglia. There was increased caspase 3 expression in both rat strains, and it was independent of the method used to induce SE. These data demonstrate that caspase 3 contributes to the cell death occurring within the first week after SE, but in only a small proportion of degenerating cells. These results suggest that, contrary to expectations, caspase 3 inhibitors would have only limited benefits in the treatment of SE.
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002452:Cell Count; D016923:Cell Death; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects*; D004789:Enzyme Activation; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005452:Fluoresceins; D005456:Fluorescent Dyes / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D009930:Organic Chemicals; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005904:Glial Fibrillary Acidic Protein; D009930:Organic Chemicals; D010446:Peptide Fragments; C435731:fluoro jade; D010447:Peptide Hydrolases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C108711:DEVDase; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid