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 member of the TNF receptor family, in cell death after focal cerebral ischemia. Focal ischemia was induced in the Sprague-Dawley rat. Evidence for apoptosis was determined by morphology as well as the presence of DNA fragmentation by the end labeling technique (TUNEL). Immunohistochemistry was performed to detect expression of both fas and fas ligand (fasL). In a separate set of experiments, two groups of mice were studied: lpr (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, there was evidence for apoptosis based on morphological criteria as well as the TUNEL technique in the rat. Immunohistochemistry demonstrated increased expression of both fas and fasL in the ischemic region, with maximal staining 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 mutant mice (lpr) had significantly smaller infarcts as compared to the wild type. 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 suggest that fas-mediated apoptosis contributes to this process.
Rosenbaum
D M
DM
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. drosenba@aecom.yu.edu
Gupta
G
G
D'Amore
J
J
Singh
M
M
Weidenheim
K
K
Zhang
H
H
Kessler
J A
JA
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000737:chemistry / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019014:fas Receptor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*
D019014:fas Receptor