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

Daniel M. Rosenbaum, Gaurav Gupta, Jason D'Amore, Manjeet Singh, Karen Weidenheim, Hong Zhang, John A. Kessler

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131 Scopus citations

Abstract

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: 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, 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 (Ipr) 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. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)686-692
Number of pages7
JournalJournal of Neuroscience Research
Volume61
Issue number6
DOIs
StatePublished - Sep 15 2000

Keywords

  • Apoptosis
  • Cerebral ischemia
  • Mice
  • Mutant
  • Rats

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Rosenbaum, D. M., Gupta, G., D'Amore, J., Singh, M., Weidenheim, K., Zhang, H., & Kessler, J. A. (2000). Fas (CD95/APO-1) plays a role in the pathophysiology of focal cerebral ischemia. Journal of Neuroscience Research, 61(6), 686-692. https://doi.org/10.1002/1097-4547(20000915)61:6<686::AID-JNR12>3.0.CO;2-7