Involvement of oxidative stress and caspase-3 in cortical infarction after photothrombotic ischemia in mice.
Apoptosis-related cell death is linked to oxidative stress and caspases in experimental cerebral ischemia. However, the role of oxidative stress in caspase activation and subsequent apoptotic cell death after cerebral ischemia is unknown. The authors evaluated the role of oxidative stress in ischemic cerebral infarction after photothrombosis and the relation between oxidative stress and caspase-related cell death 6 and 24 hours after ischemia with and without U-74389G, a potent free radical scavenger (10 mg/kg, 30 minutes before and after ischemia induction). Reactive oxygen species, detected by hydroethidine oxidation, and cytosolic cytochrome c were detected in early ischemic lesions. Western blot analysis showed the cleaved form and the increased level of the proform of caspase-3 in the ischemic lesion 24 hours after ischemia. Decreased caspase-3 immunoreactivity was detected in the antioxidant-treated group after ischemia. Decreased DNA fragmentation and laddering were detected and the lesion was smaller in the treated group after ischemia compared with the untreated group. Oxidative stress and cytochrome c release occur in the ischemic lesion after photothrombotic ischemia. The free radical scavenger attenuated caspase-3 up-regulation, DNA fragmentation, and the final lesion. The authors concluded that oxidative stress may mediate caspase-related apoptotic cell death and subsequent cortical infarction after photothrombotic ischemia.
Kim
G W
GW
Department of Neurosurgery, Stanford University School of Medicine, California, USA.
Sugawara
T
T
Chan
P H
PH
D000818:Animals; D000906:Antibodies; D000975:Antioxidants / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000502:physiology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D053938:DNA Fragmentation; D016166:Free Radical Scavengers / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D020767:Intracranial Thrombosis / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011281:Pregnatrienes / Q000494:pharmacology
D000906:Antibodies; D000975:Antioxidants; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D011281:Pregnatrienes; C074965:U 74389F; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases