  The time course of oxidative damage in different brain regions was
investigated in the gerbil model of transient cerebral ischemia. Animals were
subjected to both common carotid arteries occlusion for 5 min. After the end of
ischemia and at different reperfusion times (2, 6, 12, 24, 48, 72, 96 h and 7
days), markers of lipid peroxidation, reduced and oxidized glutathione levels,
glutathione peroxidase, glutathione reductase, manganese-dependent superoxide
dismutase (MnSOD) and copper/zinc containing SOD (Cu/ZnSOD) activities were
measured in hippocampus, cortex and striatum. Oxidative damage in hippocampus
was maximal at late stages after ischemia (48-96 h) coincident with a
significant impairment in glutathione homeostasis. MnSOD increased in
hippocampus at 24, 48 and 72 h after ischemia, coincident with the marked
reduction in the activity of glutathione-related enzymes. The late disturbance
in oxidant-antioxidant balance corresponds with the time course of delayed
neuronal loss in the hippocampal CA1 sector. Cerebral cortex showed early
changes in oxidative damage with no significant impairment in antioxidant
capacity. Striatal lipid peroxidation significantly increased as early as 2 h
after ischemia and persisted until 48 h with respect to the sham-operated
group. These results contribute significant information on the timing and
factors that influence free radical formation following ischemic brain injury,
an essential step in determining effective antioxidant intervention.
