title: Cyclooxygenase-2 expression and effect of celecoxib in flurothyl-induced neonatal seizure.
abstract: Endogenous PGE(2) dynamically regulates membrane excitability, synaptic transmission and plasticity. Neonatal seizures are associated with a number of activity-dependent changes in brain development including altered synaptogenesis and synaptic plasticity as well as reduction in neurogenesis. Thus, it is reasonable to hypothesize that alteration of cyclooxygenase-2 (COX-2) expression induced by neonatal seizure may influence brain development. We evaluated the expression of COX-2 and microsomal prostaglandin E synthase (mPGES) by Western blot analysis and immnohistochemistry in flurothyl-induced neonatal seizure and also studied the effect of celecoxib on seizure induction. Seven to 10 days old Sprague-Dawley rats were used for control (n = 18) and experimental group (n = 30). Recurrent seizure group showed more increased level of COX-2 expression than control group. However, the level of mPGES-2 expression was similar in both groups, and mPGES-1 was not detected. Hippocampus of control rats showed endogenous COX-2 expression, which was localized mainly in CA3 region. This localization pattern was similar in recurrent seizure rats, but intensity of COX-2 expression was more increased than in control rats. Celecoxib treatment significantly delayed the seizure attack and also reduced COX-2 expression. In conclusion, this study suggests that COX-2 expression is related to epileptogenesis in flurothyl-induced neonatal seizure model and shows the possibility that its inhibition lessens functional impairments that occurred in neonatal seizure.
authors.affiliation: Department of Pediatrics, and Department of Pathology, Dongguk University College of Medicine, Kyongju, Kyongbuk, Korea.
authors.forename: Doo Kwun
authors.initials: DK
authors.lastname: Kim
authors.forename: Tae Jung
authors.initials: TJ
authors.lastname: Jang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015153:Blotting, Western / Q000379:methods; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000032:analysis / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004789:Enzyme Activation; D020936:Epilepsy, Benign Neonatal / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D005481:Flurothyl; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D019746:Intramolecular Oxidoreductases / Q000032:analysis / Q000378:metabolism; D023421:Models, Animal; D000071876:Prostaglandin-E Synthases; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D005481:Flurothyl; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D000068579:Celecoxib