Differential changes of bax, caspase-3 and p21 mRNA expression after transient focal brain ischemia in the rat

Rainald Schmidt-Kastner, Jessie Truettner, Weizhao Zhao, Ludmila Belayev, Charlene Krieger, Raul Busto, Myron D. Ginsberg

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Recent studies of transient focal ischemia have focused interest on apoptotic mechanisms of neuronal cell death involving constitutive pro-apoptotic proteins. The finding of specific patterns of novel gene expression might indicate the activation of pro-apoptotic genes in previously ischemic areas. Thus, we investigated gene expression for the pro-apoptotic regulators, Bax and caspase-3, after transient focal brain ischemia, together with the p53-regulated cell cycle inhibitor, p21/WAF1/CIP1. Reversible occlusion of the middle cerebral artery for 2 h was carried out in halothane-anesthetized rats using the poly-L-lysine coated filament method. In situ hybridization was performed at 0, 1, 3, 6 h and 1, 3 and 7 d of recirculation and in sham controls. Radioactive antisense probes served for detection of bax, p21 and caspase-3 mRNAs on brain sections, and quantitative film autoradiography was combined with image-averaging techniques. Bax mRNA tended to decline after focal brain ischemia within 1 d. p21 mRNA was upregulated with a perifocal pattern at 3 h and 1 d after ischemia whereas the ischemic regions themselves failed to show significant upregulation. Caspase-3 mRNA was elevated in the resistant dorsomedial cortex at 1 d. A pro-apoptotic pattern of novel gene expression, involving Bax and caspase-3, was not observed after transient focal brain ischemia. Rather, the perifocal expression of p21 and caspase-3 mRNAs observed at 1 d after ischemia points to reactive changes in resistant brain areas. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)88-101
Number of pages14
JournalMolecular Brain Research
Volume79
Issue number1-2
DOIs
StatePublished - Jun 23 2000

Keywords

  • Apoptosis
  • Bax
  • Caspase
  • Cell cycle
  • p21

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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