Mitochondrial Susceptibility to Oxidative Stress Exacerbates Cerebral Infarction That Follows Permanent Focal Cerebral Ischemia in Mutant Mice with Manganese Superoxide Dismutase Deficiency

摘要: Mitochondrial injury has been implicated in ischemic neuronal injury. Mitochondria, producing adenosine triphosphate by virtue of electron flow, have shown to be both the sites superoxide anion (O2-) production and target free radical attacks. We evaluated these mechanisms an vivo cerebral ischemia model, using mutant mice with a heterozygous knock-out gene (Sod2 -/+) encoding mitochondrial manganese dismutase (Mn-SOD). Sod2 -/+ demonstrated prominent increase O2- under normal physiological conditions ischemia, as evidenced specific oxidation fluorescent probe, hydroethidine, reflecting decreased activity Mn-SOD. A viability assay that used rhodamine 123, which is accumulated transmembrane potential viable mitochondria, accelerated development This rapid progress resulted exacerbation infarct size hemisphere enlargement, causing advanced neurological deficits but without altering DNA fragmentation induction. The present study suggests overproduced compartment, when uncoupled from antioxidant defenses, induces impairment function causes infarction after ischemia.