EARLY GABAPENTIN TREATMENT DURING THE LATENCY PERIOD REDUCES EPILEPTOGENESIS IN AN ANIMAL MODEL OF TLE

ROSSI A; ROSCISZEWSKI G, ; RAMOS AJ

Mar del Plata

Congreso; LXI meeting de la Sociedad Argentina de Investigacion Clínica (SAIC); 2016

Sociedad Argentina de Investigacion Clinica - Sociedad Argentina de Inmunología

Temporal lobe epilepsy (TLE) affects adult population but retrospectivestudies have shown in most patients an event of febrileseizures with status epilepticus (SE) during childhood followed bya latency period (LP) until the epileptic seizures in the early adulthood.Using an animal model of TLE we have previously shownthat latency period brains presents neurodegeneration, macrophagesinfiltration and reactive gliosis. A short 4-days Gabapentin(GBP) treatment following the SE reduced neurodegeneration andreactive gliosis in the TLE model (Rossi et al 2013). GBP reducesmicroglial activation but also is an antagonist of the TPS-1 receptorprobably involved in spurious sinaptogenesis proposed as theepileptogenic process. The aim of this work was to ascertain ifthe early GBP treatment after SE is able to increase the seizuresthreshold after the LP thus preventing the epileptogenesis. Adultmale Wistar rats were subjected to the lithium-pilocarpine modelof TLE and behavioral changes were evaluated according to theRacine scale. 24 h later animals received intraperitoneally (ip)400mg GBP during 4 days. By 21 days after the SE animals wereexposed again to repeated sub-convulsive doses of pilocarpineand the development of seizures were recorded. Animals treatedwith the 4-day GBP paradigm showed a reduced SE development(34% vs. 72%), 33% of them reached lesser Racine scale levelsshowing a fast and better recovery.Our results show that earlyGBP treatment after SE not only reduced neurodegeneration,neuroinflammation and reactive gliosis, but also may have an effectpreventing the establishing of epileptic seizures after the LP.These results open the possibility of developing new treatmentstrategies for febrile seizures during the childhood.