ATTENUATION OF P53 EXPRESSION PROTECTS AGAINST FOCAL ISCHEMIC DAMAGE IN TRANSGENIC MICE

Apoptosis or programmed cell death may be involved in neuronal death i n the cerebral cortex after a permanent focal ischemic insult. Studies indicate that protein p53 is a major determinant of the cellular mech anism that leads to programmed cell death. Wild-type C57 mice and two groups of transgenic C57 mice, one homozygous and the other heterozygo us for a p53 null gene, were subjected to middle cerebral artery occlu sion. As expected, the wild-type mice had a large, consistent infarct volume (22.11 +/- 4.59 mm(3); n = 10). Both transgenic groups had sign ificantly less ischemic damage than the wild-type control group. Howev er, unexpectedly, the heterozygous group had the least amount of ische mic damage (16.12 +/- 1.71 mm(3), n = 11; 27% reduction in infarct siz e). The ischemic damage in the homozygous group (18.72 +/- 3.48 mm(3), n = 9) was significantly less than in the wild-type control (15% redu ction in infarct size) but significantly more than in the heterozygous group. Thus, although the absence of p53 expression was protective, g rater protection was afforded by reduced expression of p53. These data suggest that attenuated p53 expression may be protective after an isc hemic event.