title: The effects of simvastatin on hippocampal caspase-3 and Bcl-2 expression             following kainate-induced seizures in rats.
abstract: Status epilepticus (SE) causes neuronal loss and apoptosis by inducing several apoptosis-regulatory genes. Two such genes, cysteinyl aspartate-specific protease-3 (caspase-3), an apoptosis activator, and B-cell leukemia-2 (Bcl-2), an apoptosis suppressor, are tightly regulated for their expression and activation. Statins, inhibitors of HMG-CoA reductase, have been recently recognized as neuroprotective drugs. However, their underlying mechanisms are still unclear. In this study, we examined the neuroprotective effects of simvastatin in a rat model of SE induced by kainic acid (KA). Feeding of simvastatin for 3 days after kainate injection rescued SE-induced neuronal apoptosis, as determined by histological examination of brain sections at the level of the dorsal hippocampus. Semi-quantitative RT-PCR showed that SE treatment markedly increased caspase-3 mRNA expression and reduced Bcl-2 mRNA expression in the hippocampus. Similarly, western blot analysis and immunohistochemical analysis of the rat hippocampus demonstrated that under SE treatment, caspase-3 protein levels significantly increased and peaked at 72 h, whereas Bcl-2 protein levels decreased from 6-24 h following SE. Interestingly, simvastatin could reverse the aforementioned SE-induced changes, suggesting that the neuroprotective effects of simvastatin against neuronal apoptosis may be achieved by inhibiting caspase-3 expression and increasing Bcl-2 expression.
authors: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, PR China.
authors: Jiahang
authors: J
authors: Sun
authors: Chuncheng
authors: C
authors: Xie
authors: Wei
authors: W
authors: Liu
authors: Dunyue
authors: D
authors: Lu
authors: Weidong
authors: W
authors: Qiao
authors: Qi
authors: Q
authors: Huang
authors: Zhihui
authors: Z
authors: Huo
authors: Hong
authors: H
authors: Shen
authors: Zhiguo
authors: Z
authors: Lin
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007608:Kainic Acid; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D019821:Simvastatin / Q000494:pharmacology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D019821:Simvastatin; D053148:Caspase 3; D007608:Kainic Acid