Effect of Perampanel or Amantadine Treatment on Pilocarpine Rat Model of Status Epilepticus: Evidence with Seizure Termination, Behavioral Alterations, Epileptogenesis and Neuronal Damage.
Mohammad, Hanan omar
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Persistent activation of ionotropic glutamatergic receptors contributes to seizure sustenance and neuronal cell death. Status epilepticus (SE) was induced in adult male Sprague Dawley [12 to 14 weeks old] rats by treating them with pilocarpine. The efficacy of either perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker, or amantadine, a N-Methyl-D-aspartic acid (NMDA) receptor blocker, in overcoming pilocrapine-induced SE was assessed using electroencephalogram (EEG) recordings. In addition, the alterations in cognitive function, development of spontaneous recurrent seizures (SRSs), and hippocampal damage that are generally encountered in SE were also assessed at 72 hours and 1 month after pilocarpine treatment. Our results show that both early and late treatment with perampanel but not amantadine significantly reduced the latency in the termination of seizure as confirmed by EEG recording. Perampanel but not amantadine, reversed the memory impairment in SE rats and retarded the appearance of SRS. Fluoro-Jade C staining and NeuN immunohistochemistry revealed the protective effects of perampanel. Perampanel treatment led to reduced caspase-3 activation in the hippocampal sections of brains isolated from SE rats. In vitro addition of either perampanel or amantadine in primary cultures of hippocampal neurons significantly reduced the levels of cytotoxicity and caspase-3 activation induced by AMPA and NMDA. Both perampanel and amantadine treatment also reduced GAPDH, p53, PTEN, and active SREBP-1 levels expressed in nuclear fractions isolated from the primary cultures of hippocampal neurons treated with either AMPA or NMDA. Our data might shed some light in the therapeutic approach of perampanel in clinical use for status epilepticus
DegreeMaster of Science (M.Sc.)
CommitteeTaghibiglou, Changiz Dr.; Bardal, Stan Dr.; Tellez-Zeneto, Jose Dr.; Zhang, Yanbo Dr.
Copyright DateDecember 2018
Perampanel: Amantadine: Cognitive morbidity.