Early gabapentin treatment during the latency period reduces epileptogenesis in an animal model of TLE

ROSCISZEWSKI GERARDO; ROSSI ALICIA; RAMOS ALBERTO JAVIER

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXIV Congreso de la Sociedad Argentina de Inmunología (SAI) y XLVIII Congreso de la Sociedad Argentina de Farmacología Experimental (SAFE); 2016

Temporal lobe epilepsy (TLE) affects adult population but retrospective studies have shown in most patients an event of febrile seizures with status epilepticus (SE) during childhood followed by a latency period (LP) until the epileptic seizures in the early adulthood. Using an animal model of TLE we have previously shown that latency period brains presents neurodegeneration, macrophages infiltration and reactive gliosis. A short 4-days Gabapentin (GBP) treatment following the SE reduced neurodegeneration and reactive gliosis in the TLE model (Rossi et al 2013). GBP reduces microglial activation but also is an antagonist of the TPS-1 receptor probably involved in spurious sinaptogenesis proposed as the epileptogenic process. The aim of this work was to ascertain if the early GBP treatment after SE is able to increase the seizures threshold after the LP thus preventing the epileptogenesis. Adult male Wistar rats were subjected to the lithium-pilocarpine model of TLE and behavioral changes were evaluated according to the Racine scale. 24 h later animals received intraperitoneally (ip) 400mg GBP during 4 days. By 21 days after the SE animals were exposed again to repeated sub-convulsive doses of pilocarpine and the development of seizures were recorded. Animals treated with the 4-day GBP paradigm showed a reduced SE development (34% vs. 72%), 33% of them reached lesser Racine scale levels showing a fast and better recovery.Our results show that early GBP treatment after SE not only reduced neurodegeneration, neuroinflammation and reactive gliosis, but also may have an effect preventing the establishing of epileptic seizures after the LP. These results open the possibility of developing new treatment strategies for febrile seizures during the childhood.