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Seizure susceptibility in immature brain due to lack of COX-2-induced PGF2α.

Authors
Chung, JI; Kim, AY; Lee, SH; Baik, EJ
Citation
Experimental neurology, 249:95-103, 2013
Journal Title
Experimental neurology
ISSN
0014-48861090-2430
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.
MeSH terms
Age FactorsAnimalsAnimals, NewbornBrain/drug effects/*growth & development/*metabolismCells, CulturedCyclooxygenase 2/*biosynthesisDinoprost/administration & dosage/*biosynthesisDisease SusceptibilityGlycosylationMiceSeizures/*metabolismUp-Regulation/physiology
DOI
10.1016/j.expneurol.2013.08.014
PMID
24005111
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
이, 수환백, 은주
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