Anti-epileptogenic effect of FC99 and resveratrol

Abstract

Toll-like receptor 3 (TLR3), plays an important role in the development of epilepsy after brain insults. Previously, TLR3 deficiency in a pilocarpine model of temporal lobe epilepsy (TLE) was shown to reduce mortality, spontaneous recurrent seizures (SRS) and neuroinflammation. We hypothesized that pharmacological inhibition of TLR3 would reduce epileptogenesis following status epilepticus. We show that Resveratrol and FC99, two TLR3 blockers, demonstrate anti-epileptogenic effects in a pilocarpine model of TLE. While both Resveratrol and FC99 were previously shown to benefit in other pathologies, neither of these blockers had been proposed for the treatment of epilepsy. Our results provide substantial evidence to the importance of TLR3 inhibition in the prevention of epilepsy and specifically highlighting FC99 as a promising novel anti-epileptic drug. We anticipate our data to be a starting point for further studies assessing the anti-epileptogenic potential of FC99 and other TLR3 blockers, paving the way for pharmacological interventions that prevent epileptogenesis.