ARE ASTROCYTES INVOLVED IN THE EPILEPTOGENESIS?. THE EFFECTS OF THROMBOSPONDIN RECEPTOR BLOCKAGE IN A MODEL OF TEMPORAL LOBE EPILEPSY.

ROSSI AR; ANGELO MF; VILLARREAL A; LUKIN J; REINES AG; RAMOS AJ

Londres

Congreso; X European Congress on Epileptology.; 2012

International League against Epilepsy

The Lithium-pilocarpine model of epilepsy reproduces in rodents many of the features of human temporal lobe epilepsy (TLE) by inducing an acute period of status epilepticus (SE) followed by a variable latency period (from 7 days to several months). During the latency, several changes occur including reactive gliosis, neuronal death and neuronal network reorganization that are supposed to determine the final appearance of spontaneous recurrent seizures. The aim of this study was to determine if astrocytes are involved in the network reorganization during the latency, specifically by secreting synaptogenic thrombospondins. Using loss of function studies achieved by blocking the neuronal thrombospondins receptor α2δ1 with gabapentin (Gp) in rats exposed to the Li-pilo model of TLE, we followed the changes in neuronal circuits and reactive gliosis. Adult male Wistar rats were injected intraperitoneally (ip) with 3mEq/Kg LiCl and 20 hs later they were injected with 30 mg/Kg pilocarpine. 15 minutes after the onset of the status epilepticus (SE), seizures were finished by the injection of 10 mg/Kg diazepam. During the following 15 days animals received with 400 mg/Kg/day Gp or saline (ip). In vitro, studies were performed in mixed glio-neuronal hippocampal cultures exposed to excitotoxic glutamate and subsequent exposure to Gp (5, 25, 50 or 100 ug/ml) or vehicle. During the latency, SE animals showed reactive gliosis, neuronal degeneration, ultrastructural alterations in synapses, changes in the expression of synaptic marker synaptofisin (Syn) and increased level of PSA-NCAM in the hippocampus. Gp treatment reduced the alterations in the Syn and PSA-NCAM but was unable to change the neuronal loss and reactive gliosis. In glio-neuronal culture, Gp treatment was able to partially prevent the dendritic loss caused by glutamate but increased reactive gliosis. Taken together ours results showed that Gp-induced blockage of neuronal TSP receptor partially prevented the atypical synaptic morphology but was unable to prevent neuronal loss or reactive gliosis