《Attenuation of cerebral ischemic injury in SOD transgenic mice》.pdfVIP

Proc. Natl. Acad. Sci. USA Vol. 88, pp. 11158-11162, December 1991 Neurobiology Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase (middle cerebral artery occlusion/brain edema/superoxide radicals) HIROYUKI KINOUCHI*, CHARLES J. EPSTEINtt, TAKUJI MIZUI*, ELAINE CARLSONt, SYLVIA F. CHEN*, AND PAK H. CHAN*§1 Departments of *Neurology, §Neurosurgery, tPediatrics, and *Biochemistry and Biophysics, University of California, San Francisco, CA 94143 Communicated by John A. Clements, September 16, 1991 (receivedfor review June 28, 1991) ABSTRACT Oxygen-derived free radicals have been im- chemia in the gerbil brain (13). Liposome-entrapped CuZn- plicated in the pathogenesis of vasogenic edema and infarction SOD, which has a half life of 4.2 hr (11), reduces the severity caused by ischeria and reperfusion injury. In earlier studies, of traumatic and ischemic injuries (14, 15). exogenously supplied liposome-entrapped CuZn superoxide Although these studies provide potential therapeutic pre- dismutase (CuZn-SOD)ameliorated ischemic brain edema and cedents for the management of brain injury, alternative infarction in rats following focal cerebral ischemla. To ascer- experimental approaches are needed to address the issues of tain directly the role of SOD in the protection against super- the role ofoxygen free radicals and the mode ofaction of SOD oxide radical-induced injury, we measured infarct size and in ischemic brain injury. To investigate directly the role of water content 24 hr following focal cerebral ischemia in increased brain CuZn-SOD in the pathogenesis of brain nontransgenic mice and in transgeic mice bearing the human injuries presumed to involve superoxide radicals, we have SODI gene. These transgenic mice have 3.1-fold high