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Molecular Neurobiology

, Volume 56, Issue 4, pp 2508–2523 | Cite as

Perampanel but Not Amantadine Prevents Behavioral Alterations and Epileptogenesis in Pilocarpine Rat Model of Status Epilepticus

  • Hanan Mohammad
  • Sathiya Sekar
  • Zelan Wei
  • Farzad Moien-AfshariEmail author
  • Changiz TaghibiglouEmail author
Article
  • 291 Downloads

Abstract

Pilocarpine-induced status epilepticus (SE), which results in the development of spontaneous recurrent seizures (SRSs) activates glutamatergic receptors that contribute to seizure sustenance and neuronal cell death. In the current study, we evaluate whether the exposure to 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 would reduce the SE-induced long-term consequences. SE was induced in adult male Sprague Dawley rats with pilocarpine. Perampanel or amantadine was injected 10 or 60 min after SE onset. The efficacy of either, in overcoming pilocarpine-induced SE was assessed using electroencephalogram (EEG) recordings. In addition, alterations in cognitive function, development of spontaneous recurrent seizures (SRSs), and hippocampal damage that are generally encountered after SE were also assessed at 72 h and 5 weeks after the induction of SE. Our results indicate that both early and late treatment with perampanel but not amantadine significantly reduced seizure activity. Furthermore, perampanel but not amantadine, reversed the memory deficits in Y-maze and novel object recognition (NOR) tests and retarded the appearance of SRSs. Moreover, perampanel treatment led to reduced SE-induced caspase-3 activation in the hippocampal lysates. Taken together, the data obtained from the study reveals that blocking AMPA receptors by perampanel can modify SE-induced long-term consequences. Our results may provide a proof of principle for the potential therapeutic application of perampanel in clinical use for status epilepticus in future.

Keywords

AMPA receptor NMDA receptor Status epilepticus Spatial memory 

Notes

Funding

This work was supported by Saskatchewan Health Research Foundation (SHRF) Establishment Grant (SHRF No. 3543).

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Authors and Affiliations

  1. 1.Department of Pharmacology, College of MedicineUniversity of SaskatchewanSaskatoonCanada
  2. 2.Department of Medicine, College of MedicineUniversity of SaskatchewanSaskatoonCanada
  3. 3.Division of Neurology, Department of MedicineUniversity of British ColombiaVancouverCanada

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