MECHANISMS OF HIPPOCAMPAL REOXYGENATION INJURY

Mechanisms of 12 min of hypoxia and subsequent reoxygenation were stud ied in rat hippocampal slices. General cell injury in reoxygenation wa s indicated by increased lactate dehydrogenase (LDH). Increase in conj ugated dienes (CD) showed that oxygen radical burst induced lipid pero xidation (LPO). Am increase was also involved in reoxygenation injury, since cyanide, an inhibitor of ATP synthesis, decreased this damage. The results obtained on using inhibitors of oxygen radicals generation , i.e., allopurinol, indomethacin, rotenone, and antimycin A, strongly suggest that the sources of oxygen radicals were the xanthine/xanthin e oxidase system, prostaglandin synthesis, and mitochondrial respirato ry chain. The involvement of oxygen radicals in oxidative stress was c onfirmed also by using chain-breaking antioxidants, trolox alpha-tocop herol and stobadine, cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyrid o (4,3b)indole]. Stobadine added at the onset of reoxygenation was mos t effective, acting in a dose-dependent manner and found to be without effect when applied in hypoxia. Cytochrome-e oxidase was decreased in reoxygenated hippocampal slices treated with stobadine.