Abstracts

Rationale: Perampanel is a new antiepileptic drug acts with a new mechanism of action via non-competitive antagonism of the ionotropic a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor of glutamate, the main mediator of excitatory neurotransmission. Assuming the same underlying excitotoxicity-related brain injury mechanism of hypoxic-ischemic encephalopathy (HIE) and epilepsy, we hypothesized that perampanel would have a neuroprotective effect in HIE. Methods: We divided rats into 3 groups at each testing session: 3day-postfed and/or 1day prefed with perampanel, and postfed with saline. A hypoxic-ischemic brain injury was induced by complete disconnection of right common carotid artery in 7-day-old rats and followed by 2.5 hour of exposure to 8% oxygen. Weekly Open field tests were performed from postnatal 2nd week to 6th week, and the Morris water maze tests were performed daily in 7th week. The animals were killed on 8th week to evaluate the severity of brain damage. Results: The rate of cerebral / hippocampal infarction area were lower in pre and postfed group (12.1% / 26.8%) with perampanel 0.2 mg/kg/dose than only postfed group (31.6% / 68.4%), and saline (31.1% / 79.9%) group (P=0.021, 0.013). Spatial learning and memory function were not significantly different in groups. Conclusions: This study suggests that perampanel pretreatment exerts a neuroprotective effect on HIE in neonatal rats. The obtained results suggest that perampanel pretreatment could be used for neuroprotective treatment for neonates under hypoxic-ischemic conditions. Funding: This research was supported by a grant of the Korea Health Technology R & D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C0810).