Cyclooxygenase-2 expression and effect of celecoxib in flurothyl-induced neonatal seizure.
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.
Kim
Doo Kwun
DK
Department of Pediatrics, and Department of Pathology, Dongguk University College of Medicine, Kyongju, Kyongbuk, Korea.
Jang
Tae Jung
TJ
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*
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D005481:Flurothyl; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D000068579:Celecoxib