Effects of SC58236, a selective COX-2 inhibitor, on epileptogenesis and spontaneous seizures in a rat model for temporal lobe epilepsy

Inflammation is an important biological process that is activated after status epilepticus and could be implicated in the development of epilepsy. Here we tested whether an anti-inflammatory treatment with a selective cox-2 inhibitor (SC58236) could prevent the development of epilepsy or modify seizure activity during the chronic epileptic phase. SC58236 was orally administered (10mg/kg) during the latent period for 7 days, starting 4h after electrically induced SE. Seizures were monitored using EEG/video monitoring until 35 days after SE. Cell death and inflammation were investigated using immunocytochemistry (NeuN and Ox-42). Sprouting was studied using Timm's staining after 1 week and after 4-5 months when rats were chronic epileptic. SC58236 was also administered during 5 days in chronic epileptic rats. Hippocampal EEG seizures were continuously monitored before, during and after treatment. SC58236 effectively reduced PGE(2) production but did not modify seizure development or the extent of cell death or microglia activation in the hippocampus. SC58236 treatment in chronic epileptic rats did not show any significant change in seizure duration or frequency of daily seizures. The fact that cox-2 inhibition, which effectively reduced prostaglandin levels, did not modify epileptogenesis or chronic seizure activity suggests that this type of treatment (starting after SE) will not provide an effective anti-epileptogenic or anti-epileptic therapy. (C) 2008 Elsevier B.V. All rights reserved.