title: Seizure susceptibility in immature brain due to lack of COX-2-induced PGF2α.
abstract: The immature brain is prone to seizure; however, the mechanism underlying this vulnerability has not been clarified. Febrile seizure is common in young children, and the use of non-steroidal anti-inflammatory drugs for febrile seizure is not recommended. In previous studies, we established that prostaglandin (PG) F2α, a product of cyclooxygenase (COX), acts as an endogenous anticonvulsant in the adult mouse. Therefore, we assumed that COX-2 activity was involved with seizure susceptibility in early life. In the present study, immature mice (postnatal day 9) were far more prone to kainic acid (KA)-induced seizures than mature mice (after postnatal day 35). Seizure activity began later in immature mice, but was more severe and was unaffected by a potent COX inhibitor, indomethacin; in contrast, indomethacin aggravated seizure activity in mature mice. Immature mouse brains exhibited little basal COX-2 expression and little KA-induced COX-2 induction, while KA-induced COX-2 expression and PGF2α release were prominent in mature brains. During brain development, COX expression was increased and glycosylated in an age-dependent manner, which was necessary for COX enzyme activity. Intracisternal PGF2α administration also reduced KA-induced seizure activity and mortality. Taken together, low COX activity and the resulting deficiency of PGF2α may be an essential cause of increased seizure susceptibility in the immature brain.
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea; Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jee-In
authors.initials: JI
authors.lastname: Chung
authors.forename: A Young
authors.initials: AY
authors.lastname: Kim
authors.forename: Soo Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Baik
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015237:Dinoprost / Q000008:administration & dosage / Q000096:biosynthesis*; D004198:Disease Susceptibility; D006031:Glycosylation; D051379:Mice; D012640:Seizures / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015237:Dinoprost; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Cyclooxygenase; Developing brain; Prostaglandin F(2α); Seizure