SUSTAINED INDUCTION OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE-2 BY SEIZURES IN HIPPOCAMPUS - INHIBITION BY A PLATELET-ACTIVATING-FACTOR ANTAGONIST

Prostaglandin G/H synthase-2 and zif-268 mRNA expression is transientl y induced in rat brain by kainic acid (KA)-induced seizures and by a s ingle electroconvulsive shock. Induction of both genes by KA shows neu roanatomical specificity in the order hippocampus > cerebral cortex > striatum > brain stem > cerebellum. Nuclear run-on and Western blottin g shows that both genes are transcriptionally activated, and that kain ic acid up-regulation of prostaglandin G/H synthase-2 mRNA expression in hippocampus matches increased protein levels. Whereas the magnitude of hippocampal zif-268 mRNA induction is similar in both seizure mode ls, peak induction of prostaglandin G/H synthase-2 mRNA is 7-fold grea ter in the kainic acid model than in the electroconvulsive shock model and is much more prolonged. Pretreatment of animals by intracerebrove ntricular injection with the intracellular platelet-activating factor receptor antagonist BN 50730 strongly attenuates kainic acid and elect roconvulsive shock induction of prostaglandin G/H synthase-2 expressio n. The drug partially inhibits electroconvulsive shock induction of zi f-268, but is relatively ineffective against kainic acid-induced zif-2 68 expression. Seizure-induced expression of both genes involves plate let-activating factor, but the mechanisms of induction must be otherwi se distinct. The selectively elevated induction of hippocampal prostag landin G/H synthase-2 by kainic acid correlates with a neuroanatomical region in which the agonist induces neuronal damage.