Several studies have demonstrated that ischemic preconditioning increases
superoxide dismutase activity, but it is unclear how ischemic preconditioning affects events downstream of
hydrogen peroxide production during subsequent severe
ischemia and reperfusion in the hippocampus. To answer this question, we investigated whether ischemic preconditioning in the hippocampal CA1 region increases the activities of
antioxidant enzymes glutathione peroxidase and
catalase, resulting in a decrease in the level of
hydroxyl radicals during subsequent severe
ischemia-reperfusion. Transient forebrain
ischemia was induced by four-vessel occlusion in rats. Ischemic preconditioning for 3 min or a
sham operation was performed and a 15-min severe
ischemia was induced three days later. Ischemic preconditioning preserved the CA1 hippocampal neurons following severe
ischemia. The concentration of
2,3-dihydroxybenzoic acid, an
indicator of
hydroxyl radical, was measured using in vivo microdialysis technique combined with HPLC. The
ischemia-induced increase in the ratio of
2,3-dihydroxybenzoic acid concentration relative to baseline did not differ significantly between preconditioned and control groups. On the other hand, activities of the
antioxidant enzymes glutathione peroxidase-1 and
catalase were significantly increased at 3 days after ischemic preconditioning in the hippocampus. Our results suggest that, in preconditioned rats, while
hydrogen peroxide is generated from severe
ischemia, the activity of
catalase and
glutathione peroxidase-1 is correspondingly increased to eliminate the excessive
hydrogen peroxide. However, our results show that the enhanced activity of these
antioxidant enzymes in preconditioned rats is not sufficient to decrease
hydroxyl radical levels during subsequent severe
ischemia-reperfusion.