Nonischemic and ischemic cortex from both wild-type mice (A, B) and Sod2 −/+ mice (C, D). A,C, Cytochrome c immunoreactivity was barely seen in the nonischemic specimens from both the wild-type (A) and Sod2 −/+ (C) mice. B,D, Two hours after ischemia, enhanced cytosolic immunoreactivity of cytochrome c was demonstrated in Sod2 −/+ mice (D) compared with wild-type mice (B). At this time point, diffuse cytosolic immunoreactivity was shown in the wild-type mice, whereas a strong vesicular immunoreactivity, as well as diffuse cytosolic expression, was observed in the Sod2 −/+ mice. E, F, Cytosolic cytochrome c was also observed in the z-VAD.FMK-treated mice (F, arrowheads) as well as in the vehicle-treated animals (E, arrowheads) 2 hr after ischemia. Scale bars: A, C,E, F, 20 μm; B,D, 50 μm; small boxes inB, D, 10 μm.