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.