Roberto Di Maio
Purdue University, USA
Title: Post-status epilepticus treatment with the cannabinoid agonist WIN55,212-2 prevents chronic epileptic hippocampal damage in rats
Biography
Biography: Roberto Di Maio
Abstract
Repeated seizures are often associated with development of refractory chronic epilepsy, the most common formof which is temporal lobe epilepsy. G-protein-coupled cannabinoid receptors (CB1 and CB2 receptors) regulateneuronal excitability and have been shown to mediate acute anticonvulsant effects of cannabinoids in animalmodels. However, the potential of cannabinoids to prevent chronic neuronal damage and development ofepilepsy remains unexplored. We hypothesized that treatment with a CB receptor agonist after an episode ofstatus epilepticus – but before development of spontaneous recurrent seizures – might prevent the developmentof functional changes that lead to chronic epilepsy. Using the rat pilocarpinemodel, a therapeutic approach wassimulated by administering the CB agonist,WIN55,212-2 after an episode of status epilepticus. Epileptic behaviorwas monitored during development of spontaneous recurrent seizures for up to 6 months. Histology,neurochemistry, redox status and NMDA receptor subunit expression were assessed at 6 months afterpilocarpine-induced seizures. Sub-acute treatment with WIN 55,212-2 (for 15 days starting 24 h after PILOinjection) dramatically attenuated the severity, duration and frequency of spontaneous recurrent seizures. Further, in contrast to vehicle-treated animals, hippocampi fromWIN 55,212-2-treated animals showed: normalthiol redox state, normal NR2A and NR2B subunit expression, preservation of GABAergic neurons and preventionof abnormal proliferation of GABAergic progenitors. This study shows for the first time that, after a knowninciting event, treatmentwith a compound targeting CB receptors has the potential to prevent the epileptogenicevents that result in chronic epileptic damage.