Abstract
Oxygen radicals, produced in mitochondria, are implicated in the pathogenesis of ischemic brain injury. We determined the role of manganese-superoxide dismutase (Mn-SOD) in cerebral ischemia, using mutant mice with decreased activity of Mn-SOD (Sod2 -/+). Sod2 -/+ and its littermate wild type mice were subjected to permanent middle cerebral artery occlusion. Mitochondrial viability assay demonstrated accelerated development of mitochondrail injury in Sod2 -/+. Sod2 -/+ showed advanced neurological deficits and exacerbated infarct size without altering DNA fragmentation induction. The present study suggests that mitochondrial susceptibility to oxidative stress induces mitochondrial impairment causing energy failure, and results in exacerbation of ischemic brain injury through necrotic pathway.
