Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase.

Authors: Kinouchi H; Epstein CJ; Mizui T; Carlson E; Chen SF; Chan PH

Abstract: Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.

Keywords: Animals; Ascorbic Acid/analysis; Body Water/physiology; Brain/*physiopathology; Brain Chemistry; Cerebral Cortex/chemistry/pathology; Cerebral Infarction/pathology/physiopathology; Glutathione/analysis; Humans; Ischemic Attack, Transient/genetics/*physiopathology; Male; Mice; Mice, Transgenic; Superoxide Dismutase/*genetics/physiology
Journal: Proceedings of the National Academy of Sciences of the United States of America
Volume: 88
Issue: 24
Pages: 11158-62
Date: Dec. 15, 1991
PMID: 1763030
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Citation:

Kinouchi H, Epstein CJ, Mizui T, Carlson E, Chen SF, Chan PH (1991) Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. Proceedings of the National Academy of Sciences of the United States of America 88: 11158-62.



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