Febrile seizures (FSs) are the most common convulsive seizure in early childhood. About 30% of them are “complex”, with repetitive seizures, and related to adult temporal lobe epilepsy (TLE). In this study, we investigated the role of membrane-associated prostaglandin E synthase-1 (mPGES-1), an inducible terminal enzyme for PGE₂ synthesis, in hippocampal inflammation induced by repetitive FSs (RFSs) in mouse pups as a model of complex FSs.
Wild-type (WT) and mPGES-1 knockout (ES1KO) mice at P9-11 were given intraperitoneal injections of lipopolysaccharide (100 µg/kg) and exposed to heat lamp to induce hyperthermia and FSs. The induction of FSs was repeated twice at 4 h-interval (RFSs).
In WT mice, mPGES-1 mRNA was significantly up-regulated in hippocampus after RFSs. The production of hippocampal PGE₂ observed after RFSs in WT mice was completely absent in ES1KO mice. The seizure score and increase in rectal temperature during the hyperthermia induction in ES1KO mice were slightly but significantly lower than those in WT mice. The inductions of IL-1β, TNF-α and GFAP observed significantly in WT mice were less in ES1KO mice even in which the seizure scores were almost the same level.
These results suggest that mPGES-1 contributes to inflammatory hyperthermia, convulsive events, glial activation and production of inflammatory cytokines through PGE₂ production in hippocampus. Thus, mPGES-1 may contribute to the complex FSs-induced adulthood TLE and may be a potential therapeutic target for the development of epilepsy after RFSs.