TY - JOUR
T1 - Differential changes of bax, caspase-3 and p21 mRNA expression after transient focal brain ischemia in the rat
AU - Schmidt-Kastner, Rainald
AU - Truettner, Jessie
AU - Zhao, Weizhao
AU - Belayev, Ludmila
AU - Krieger, Charlene
AU - Busto, Raul
AU - Ginsberg, Myron D.
N1 - Funding Information:
We are grateful to Dr. S.J. Elledge, Baylor College, Houston, for providing the cDNA probe for p21/CIP1. We thank Ms. Yolanda Loor for meticulous work. These studies were supported by US Public Health Service grant NS 05820.
PY - 2000/6/23
Y1 - 2000/6/23
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Bax
KW - Caspase
KW - Cell cycle
KW - p21
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U2 - 10.1016/S0169-328X(00)00104-2
DO - 10.1016/S0169-328X(00)00104-2
M3 - Article
C2 - 10925146
AN - SCOPUS:0034705558
VL - 79
SP - 88
EP - 101
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -