The COX-2 inhibitor parecoxib is neuroprotective but not antiepileptogenic in the pilocarpine model of temporal lobe epilepsy

Abstract

The enzyme cyclooxygenase-2 (COX-2), which catalyzes the production of pro-inflammatory prostaglandins, is induced in the brain after various insults, thus contributing to brain inflammatory processes involved in the long-term consequences of such insults. Mounting evidence supports that inflammation may contribute to epileptogenesis and neuronal injury developing after brain insults. Anti-inflammatory treatments, such as selective COX-2 inhibitors, may thus constitute a novel approach for anti-epileptogenesis or disease-modification after brain injuries such as head trauma, cerebral ischemia or status epilepticus (SE). However, recent rat experiments with prophylactic administration of two different COX-2 inhibitors after SE resulted in conflicting results. In the present study, we evaluated whether treatment with parecoxib, a pro-drug of the highly potent and selective COX-2 inhibitor valdecoxib, alters the long-term consequences of a pilocarpine-induced SE in rats. Parecoxib was administered twice daily at 10 mg/kg for 18 days following SE. Five weeks after termination of treatment, spontaneous recurrent seizures were recorded by continuous video/EEG monitoring. Prophylactic treatment with parecoxib prevented the SE-induced increase in prostaglandin E 2 and reduced neuronal damage in the hippocampus and piriform cortex. However, the incidence, frequency or duration of spontaneous seizures developing after SE or the behavioral and cognitive alterations associated with epilepsy were not affected by parecoxib. Only the severity of spontaneous seizures was reduced, indicating a disease-modifying effect. These results substantiate that COX-2 contributes to neuronal injury developing after SE, but inhibition of COX-2 is no effective means to modify epileptogenesis.