Fas (CD95/APO-1) plays a role in the pathophysiology of focal cerebral ischemia

The purpose of this study was to investigate the role of fas antigen, a mem ber of the TNF receptor family, in cell death after focal cerebral ischemia . Focal ischemia was induced in the Sprague-Dawley rat, Evidence for apopto sis was determined by morphology as well as the presence of DNA fragmentati on by the end labeling technique (TUNEL), Immunohistochemistry was performe d to detect expression of both fas and fas ligand (fasL), In a separate set of experiments, two groups of mice were studied: Ipr (that have a loss of function mutation for fas) and wild type. Infarct volume was measured at 24 hr as well as evidence for apoptosis. Twenty-four hours after ischemia, th ere was evidence for apoptosis based on morphological criteria as well as t he TUNEL technique in the rat. Immunohistochemistry demonstrated increased expression of both fas and fast in the ischemic region, with maximal staini ng occurring between 24-48 hr for both. Twenty-four hours after ischemia in the mice, there was evidence of apoptosis in both groups, however, the mut ant mice (Ipr) had significantly smaller infarcts as compared to the wild t ype, There was no difference in the cerebrovasculature of the two groups of mice. These data support the hypothesis that apoptosis plays a role in the pathophysiology of focal cerebral ischemia, Furthermore, these data sugges t that fas-mediated apoptosis contributes to this process. (C) 2000 Wiley-L iss, Inc.