Increase in p53 protein expression following cortical infarction in the spontaneously hypertensive rat

Using stroke-prone spontaneously hypertensive (SH-SP) rats with permanent o cclusion of the middle cerebral artery (MCA), we investigated the expressio n of wild type p53 (wt-p53) protein and the occurrence of DNA fragmentation in cerebral neurons after ischemia. Three days following MCA occlusion, te rminal deoxynucleotidyltransferase-mediated dUTP-biocin nick end labeling ( TUNEL staining) revealed a distinct pattern of nuclear staining in many neu rons around the ischemic core. On the lesioned side of the cerebral cortex one day after MCA occlusion, wt-p53 immunoreactivity was observed specifica lly in the cortical neurons, in the same regions as the TUNEL staining. Mut ant type p53 (mt-p53) immunoreactivity was not observed at any time followi ng MCA occlusion. These findings suggest that wt-p53 dependent cell death o f cortical neurons occurred in the ischemic periphery following cerebral is chemia and that this pathway for the induction of cell death may play an im portant role in the exaggeration of cerebral ischemic injury. (C) 1999 Else vier Science B.V. All rights reserved.