Cyclooxygenase-2 Inhibitor, Celecoxib, Reduces The Elevation Of Brain Cox-2,Glu Content And Prevents Seizures Following Pilocarpine-induced Status Epilepticus

Objective:As an immunity correlated disease,the development of epilepsy have close relation with many cytokines.Cyclooxygenase(COX) enzymes are critical regulators of the inflammatory and immune response.Recent findings demonstrate that COX enzymes are of primary importance in the brain's unique inflammatory response,and these play determinant roles in the status epilepticus.Cyclooxygenase-2 is expressed at low levels in a subset of neurons in CNS and is rapidly induced by a multiplicity of factors including seizure activity.A putative relationship exists between cyclooxygenase-2 induction and glutamatergic neurotransmission. These data indicate that cyclooxygenase-2 induction in a neuronal network can be a useful marker for pathways associated with seizure activity.Thus we used COX-2 immunoexpression in our pilocarpine model of status epilepticus as a marker for glutamatergic activation in the epileptic brain.In this study we evaluated cyclooxygenase-2 protein immunocytochemically and found markedly enhanced immunostaining primarily in hippocampal regions at 12h,24 h,72h and 7days following pilocarpine -induced status epilepticus.Moreover,COX isozymes are the targets of non-steroidal anti-inflammatory drugs(NSAIDs) and may be of therapeutic value after neural injury.Up-regulated brain COX-2 and increased abundance of the major COX-2-generated PGE2 are associated with the recurrence of hippocampal seizures,suggesting a potential role for COX-2-selective NSAIDs in epilepsy management.Methods:Male Wistar rats were used for epileptic rats(n=8) and normal controls(n=32)and celecoxib group(n=32).Epileptic rats were generated by lithium-pilocarpine induced SE. Lithium chloride(127mg/kg,i.p.,Sigma) was injected 24 h prior to the administration of pilocarpine.For the rats developing SE,we controlled the duration of SE by i.p.injection of diazepam(10 mg/kg).Normal control rats were only treated with saline.30 min prior to pilocarpine,celecoxib rats were fed with celecoxib,dissolved in phosphate-buffered saline(10 mg/kg).The rats were sacrificed at 12h,24 h,72h and 7days after SE for analysis of immunoexpression in brain.Resuis:Compared with the model group,the epileptic seizure was clearly inhibited in the celecoxib group.Compared with the normal control group,the cox-2 expression in hippocampus and cortex in the model group were significant in rats after 12h,started decreased 3 days after SE,returned to basal levels 7 days after SE.The activity of cox-2 and Glu in brain in the celecoxib group were a little lower than the model group.The cox-2 and Glu expression in hippocampus and cortex were analyzed with regression analysis.P values＜0.05 were considered significant.Conclusion:The epileptic seizure induced by lithium-pilocarpine can be inhibited by using celecoxib.The present results indicate that celecoxib can restrain oxidative damage from the seizure.And it can affect the cox-2 expression,and can control the glutamate release.