P53-IMMUNOREACTIVE PROTEIN AND P53 MESSENGER-RNA EXPRESSION AFTER TRANSIENT MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Background and Purpose We investigated the temporal distribution of the p53-immunoreactive protein in conjunction with cellular damage and the expression of the p53 mRNA after focal cerebral ischemia in rats. Methods Male Wistar rats (n=66; controls, n=7) were subjected to 2 hours of middle cerebral artery occlusion and were killed at various times of reperfusion (0.5 to 168 hours) for p53 immunohistochemistry and Northern blot analysis. Results A cellular expression of mutant p53-immunoreactive protein was found localized to anatomic sites exhibiting severe neuronal damage. A maximal induction of mutant p53-immunoreactive protein was found at 12 hours after reperfusion and subsequently declined. No wild-type p53 protein expression was detected after ischemia. A time-dependent expression of p53 mRNA was observed in both hemispheres. The peak level of p53 mRNA occurred at 24 hours after reperfusion. Conclusions Our data indicate that the expressions of p53-immunoreactive protein and p53 mRNA are upregulated after transient focal cerebral ischemic insult in rats. The concomitant appearance of p53 and cell damage in ischemic brain suggests that p53 expression may impact response to an ischemic insult.