Reduction of copper, zinc-superoxide dismutase in knockout mice does not affect edema or infarction volumes and the early release of mitochondrial cytochrome c after permanent focal cerebral ischemia.
Copper,zinc-superoxide dismutase (SOD1) was shown to be highly protective against ischemia/reperfusion injury in the brain. We have recently reported that SOD1 prevents the release of mitochondrial cytochrome c and subsequent apoptosis after ischemia/reperfusion in mice. To investigate its dose dependent effect on permanent focal cerebral ischemia, we examined neurological deficit scores, infarction volume, and the amount of hemisphere enlargement after 24 h of focal cerebral ischemia in both knockout mutants of SOD1 (Sod1 -/+ and Sod1 -/-) and wild-type littermates. We also examined the release of cytochrome c and subsequent DNA fragmentation after ischemia. There were no differences in the neurological deficit scores, infarction volumes and edema formation. There was also no difference of the amount cytosolic cytochrome c at 2 h and of the amount of DNA fragmentation at 24 h after focal cerebral ischemia. The results indicate that the SOD1 enzyme does not appear to affect cerebral infarction, cerebral edema nor the mitochondrial signaling pathway for apoptosis following permanent focal cerebral ischemia where there is no reperfusion injury.
Fujimura
M
M
Department of Neurosurgery, Stanford University School of Medicine, 1201 Welch Road, MSLS P304, Stanford, CA 94305-5487, USA.
Morita-Fujimura
Y
Y
Copin
J
J
Yoshimoto
T
T
Chan
P H
PH
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D001929:Brain Edema / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D002545:Brain Ischemia / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D002544:Cerebral Infarction / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D003574:Cytochrome c Group / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D006579:Heterozygote; D006720:Homozygote; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D020768:Middle Cerebral Artery / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000172:deficiency* / Q000235:genetics
D003574:Cytochrome c Group; D013482:Superoxide Dismutase