Abstracts

Rationale: Glutamatergic excitotoxicity is a key factor of epileptogenesis after status epilepticus. The goals of our study are (i) to assess the anti-epileptogenic effect of perampanel, a glutamatergic antagonist in lithium-pilocarpine model of mesial temporal lobe epilepsy in adult rats (ii) to study the temporal course of cerebral regional glucose metabolism modifications induced by lithium-pilocarpine status and their modulation by perampanel. Methods: 47 adult Sprague Dawley rats were divided into 3 groups: Control (C) (n=7) that received only lithium injection, Status Epilepticus (SE) (n=21) that experienced lithium-pilocarpine induced SE, and SE-perampanel (SE-P) (n=19) that received intragastric administration of perampanel (8 mg/kg/day) from 15 min after lithium-pilocarpine SE onset to day 8 (n=19). 18F-FDG PET imaging were performed sequentially the day before SE (D-1), 4 hours (H4), 2 days (D2) and 8 days (D8) after status onset. Animals were video-monitored from D8 to D60 to detect spontaneous recurrent seizures (Racine Stage 5) that define chronic epilepsy.  Results: 87% (n=18) SE rats became epileptic vs only 33% (n=6) SE-P. Compared to C, SE group exhibited early (H4) transient glucose hypermetabolism in hippocampal and parahippocampal cortices, caudate nucleus, motor cortex and substantia nigra followed at D2 and D8 by hypometabolism in the same structures.   Interestingly compared to epileptic rats, perampanel treated rats that did not become epileptic exhibited a significantly lower hypometabolism at D8, especially in hippocampal and parahippocampal cortices, thalamus, substantia nigra, sensorimotor cortices and caudate nucleus.  Conclusions: Perampanel, a glutamatergic antagonist, prevents epileptogenesis in about two third of adult rats submitted to lithium-pilocarpine induced SE. This effect is predicted by the down-modulation of late cerebral regional glucose hypometabolism after the status in key structures of the model. Funding: None