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

被引:37
作者
Schmidt-Kastner, R [1 ]
Truettner, J [1 ]
Zhao, WZ [1 ]
Belayev, L [1 ]
Krieger, C [1 ]
Busto, R [1 ]
Ginsberg, MD [1 ]
机构
[1] Univ Miami, Sch Med, Dept Neurol, Cerebral Vasc Dis Res Ctr, Miami, FL 33101 USA
来源
MOLECULAR BRAIN RESEARCH | 2000年 / 79卷 / 1-2期
关键词
apoptosis; Bax; caspase; p21; cell cycle;
D O I
10.1016/S0169-328X(00)00104-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:88 / 101
页数:14
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