Role of PPAR modulators on seizure control and neurobehavior in status epilepticus model in rats

Abstract This study explored the impact of peroxisome proliferator-activated receptor modulators (PPAR-m) on seizure control and epileptogenesis in a lithium-pilocarpine-induced status epilepticus (SE) model in Wistar rats. Following optimal dose determination, the effects of fenofibrate, pemafibrate, and saroglitazar alone and with antiseizure medications were examined, including seizure evaluation and neurobiological assessments on day-21 post-SE induction. The optimal doses found for fenofibrate, pemafibrate, and saroglitazar were 200, 1.5, and 3 mg/kg, respectively. Drug-treated groups exhibited improved seizure control, memory-impairment attenuation, reduced neurodegeneration, astrocyte activation, myelin, and axonal damage, along with elevated protein (PPAR-α and HMGCS2) expression, and lower levels of epileptogenesis markers compared to SE-control (p<0.001). Perampanel+PPAR-m and fenofibrate+valproate exerted improved seizure control, lesser neurodegeneration, reactive astrocytes, and higher HMGCS2 protein expression compared to ASMs alone. PPAR-m adjuvant therapy with valproate and perampanel has significant seizure control and neuroprotective potential as compared to ASM alone treatment in SE.