CONICET | Buscador de Institutos y Recursos Humanos

Epilepsy affects 1% of the world population and usually requires chronic pharmacological treatment. An important percentage of patients with temporal lobe epilepsy (TLE) refer the antecedent of an initial precipitating event (IPE) usually febrile seizure, during childhood, followed by a latency period (LP) until the onset of the chronic epileptic seizures. Gabapentin (GBP) is an antiepileptic drug useful as a coadjuvant in the treatment of refractory epilepsy and especially in treatment of neuropathic pain. In an experimental model of temporary lobe epilepsy (TLE) achieved by the lithium-pilocarpine administration; we have previously shown that during LP occur neurodegeneration, reactive gliosis and macrophages infiltration in the brain hippocampus and pyriform cortex. Gabapentin treatment successfully reduced neuronal degeneration and reactive gliosis (Rossi et al., 2013, PLOS One). In this work, we determined the GBP effects when subacutely administered for a short period of time (4 days) following the experimental IPE. Male Wistar rats were treated with by lithium-pilocarpine (127 mg/kg and 30 mg/kg respectively) developing an status epilepticus (IPE) that were limited to 20 min by 20 mg/kg diazepam administration. 24 h later animals received GBP (400 mg/kg/d) for 4 days. This treatment reduced the reactive microgliosis and changed the microglial phenotype towards a less pro-inflammatory morphology. When the GBP-treated animals were exposed to repeated pilocarpine subconvulsive doses, 21 days after the IPE, we observed that epileptic threshold was increased compared with vehicle-treated animals. Our results show that an early pharmacological intervention after the IPE is able to alter the neurodegeneration and reactive gliosis that are the biological substrate of epileptogenesis.