Hydroxyl radical production and lipid peroxidation paralles selective post‐ischemic vulnerability in gerbil brain

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Abstract
The salicylate trapping method was used to investigate the changes in hydroxyl radical (·OH) levels in the selectively vulnerable hippocampus compared to the cerebral cortex of gerbils subjected to a 10 min period of near complete forebrain ischemia. Salicylate-derived 2,5-dihydroxybenzoic acid (2,5-DHBA) was measured in sham-operated animals and at 1, 5, and 15 min of reperfusion. A basal level of 2,5-DHBA was also seen in non-ischemic gerbil brain, both in the hippocampus and cortex. The hippocampal basal level was 160% higher than in the cortex (P < .01). Treatment with the cytochrome P450 inhibitor SKF-525A (50 mg/kg s.c. 30 min before measurement) did not affect this basal level in either hippocampus or cortex, which argues against a contribution of metabolic salicylate hydroxylation as its source. In contrast, pretreatment with the arachidonic acid cyclo-oxygenase inhibitor ibuprofen (20 mg/kg s.c.) decreased (−68.8%) the level of salicylate hydroxylation in the hippocampus, but not the cortex. In animals subjected to 10 min of forebrain ischemia, a selective increase in 2,5-DHBA was observed in the hippocampus at 1 min of reprerfusion which subsided by 5 min. No increase in salicylate hydroxylation was apparent in the cortex within the same time frame. The increase in ·OH in the hippocampus at 1 min of reperfusion was accompanied by a significant decrease (−15%; P < .03) in the hippocampal levels of vitamin E. No loss of vitamin E was observed in the cortex at the same time. It is hypothesized that the selective ischemic vulnerability of the hippocampus is mechanistically related to a selective post-ischemic burst in ·OH in that region. Moreover, this may be based upon an intrinsically higher level of oxidative stress in that region as a by-product of greater arachidonic acid turnover.