Liposome-entrapped superoxide dismutase reduces cerebral infarction in cerebral ischemia in rats.
We studied the role of superoxide radicals in the pathogenesis of ischemic brain injury using a model of focal cerebral ischemia in 102 rats and liposome-entrapped CuZn-superoxide dismutase, which can penetrate the blood-brain barrier and cell membranes efficiently. The bolus intravenous administration of 25,000 units of liposome-entrapped CuZn-superoxide dismutase elevated superoxide dismutase activities in the blood and brain 1, 2, 8, and 24 hours later as well as in the ischemic hemisphere and contralateral cortex. Determined 24 hours after right middle cerebral and bilateral common carotid artery occlusion by the lack of staining for mitochondrial dehydrogenase activity with 2,3,5-triphenyltetrazolium chloride, infarct sizes were reduced by 33%, 25%, and 18% in the anterior, middle, and posterior brain slices, respectively, by treatment with liposome-entrapped CuZn-superoxide dismutase. Our data demonstrate that superoxide radicals are important determinants of infarct size following focal cerebral ischemia and that liposome-entrapped CuZn-superoxide dismutase may have pharmacologic value for the treatment of focal cerebral ischemic injury.
Department of Neurology, University of California, School of Medicine, San Francisco 94143.
S
S
Imaizumi
V
V
Woolworth
R A
RA
Fishman
P H
PH
Chan
D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology*; D003300:Copper / Q000494:pharmacology; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D004337:Drug Carriers; D008081:Liposomes; D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc