A possible role of endogenously formed cerebral prostaglandins in the development of adaptive protection against cerebral hypoxia/ischemia in mice.

We found recently that exogenously administered PGD2, PGE1 and PGI2 showed a protective effect against cerebral hypoxia/ischemia in mice. In the present study, to find out whether these PGs play a pathophysiological role in cerebral hypoxia/ischemia, we examined a possible role of PGs in the development of adaptive protection against cerebral hypoxia/ischemia. Mice were pretreated with a sublethal dose of KCN, hypoxic gas mixture and electroshock 10-120 min before tests. Ten to thirty min after pretreatment with a sublethal dose of KCN, mice proved to be significantly protected against cerebral hypoxia/anoxia in all models studied: KCN-induced anoxia, normobaric hypoxia and decapitation-induced gasping. Similar results were observed when hypoxic gas and electroshock were used as pretreatments. These facts indicate that the protective effect does not depend on how cerebral hypoxia/anoxia is induced but on the substances formed in the brain after hypoxia/anoxia as well as electroshock. Brain concentrations of cyclooxygenase products markedly increased subsequent to hypoxia/anoxia as well as electroshock. The increase in PGs formation as well as resistance to hypoxia was prevented by pretreatment with indomethacin. These findings suggest that endogenously formed PGs at least including the three PGs, PGD2, PGE1 and prostacyclin in mouse brain during or after hypoxia/ischemia are responsible for the increase of resistance to hypoxia/ischemia.