Involvement of oxidative stress and caspase-3 in cortical infarction afterphotothrombotic 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 ca spase activation and subsequent apoptotic cell death after cerebral ischemi a is unknown. The authors evaluated the role of oxidative stress in ischemi c cerebral infarction after photothrombosis and the relation between oxidat ive stress and caspase-related cell death 6 and 24 hours after ischemia wit h and without U-74389G, a potent free radical scavenger (10 mg/kg, 30 minut es before and after ischemia induction). Reactive oxygen species, detected by hydroethidine oxidation, and cytosolic cytochrome c were defected in ear ly ischemic lesions. Western blot analysis showed the cleaved form and the increased level of the preform of caspase-3 in the ischemic lesion 24 hours after ischemia. Decreased caspase-3 immunoreactivity was detected in the a ntioxidant-treated group after ischemia. Decreased DNA fragmentation and la ddering were detected and the lesion was smaller in the treated group after ischemia compared with the untreated group. Oxidative stress and cytochrom e c release occur in the ischemic lesion after photothrombotic ischemia. Th e free radical scavenger attenuated caspase-3 up-regulation, DNA fragmentat ion, and the final lesion. The authors concluded that oxidative stress may mediate caspase-related apoptotic cell death and subsequent cortical infarc tion after photothrombotic ischemia.