Abstracts

Rationale: Pilocarpine induces status epilepticus (SE) is associated with development of Spontaneous recurrent seizures (SRSs), activation of glutamatergic receptors leading to seizure persistence and neuronal death. In this study, we evaluate whether the treatment with perampanel, an a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker, or amantadine, a N-Methyl-D-aspartic acid (NMDA) receptor blocker would reduce the long-term adverse effects of SE.  Methods: We induced SE in adult male Sprague Dawley rats with pilocarpine. Perampanel or amantadine was injected 10 min or 60 min after SE onset. Seizure duration was monitored by electroencephalogram (EEG) recordings. In addition, we assessed alterations in cognitive function, development of spontaneous recurrent seizures (SRSs), and hippocampal damage at 72 hours and 5 weeks after the induction of SE. Results: Our results indicate that both early and delayed treatment with perampanel but not amantadine lead to significant reduction in time required for seizure termination as confirmed by EEG recording. In addition, perampanel but not amantadine, reduced SE-related acute neuronal injury, presented the memory dysfunction in Y-maze and novel object recognition (NOR) tests and aborted the appearance of SRSs. Moreover, caspase-3 activation by SE was reduced in the hippocampal lysates of perampanel treated rats. Conclusions: In concert, our data indicates that blocking AMPA receptors by perampanel can abort SE-induced long-term cognitive consequences. Our results may provide a proof of principle for the potential therapeutic application of perampanel early in the course of human status epilepticus in future. Funding: Supported by Saskatchewan Health Region Foundation (SHRF)