Abolishing spontaneous epileptiform activity in human brain tissue through AMPA receptor inhibition

Ann Clin Transl Neurol. 2020 Jun;7(6):883-890. doi: 10.1002/acn3.51030. Epub 2020 May 19.

Abstract

Objective: The amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is increasingly recognized as a therapeutic target in drug-refractory pediatric epilepsy. Perampanel (PER) is a non-competitive AMPAR antagonist, and pre-clinical studies have shown the AMPAR-mediated anticonvulsant effects of decanoic acid (DEC), a major medium-chain fatty acid provided in the medium-chain triglyceride ketogenic diet.

Methods: Using brain tissue resected from children with intractable epilepsy, we recorded the effects of PER and DEC in vitro.

Results: We found resected pediatric epilepsy tissue exhibits spontaneous epileptic activity in vitro, and showed that DEC and PER inhibit this epileptiform activity in local field potential recordings as well as excitatory synaptic transmission.

Interpretation: This study confirms AMPAR antagonists inhibit epileptiform discharges in brain tissue resected in a wide range of pediatric epilepsies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anticonvulsants / pharmacology*
  • Brain / drug effects
  • Child
  • Child, Preschool
  • Decanoic Acids / pharmacology*
  • Drug Resistant Epilepsy / drug therapy
  • Drug Resistant Epilepsy / pathology
  • Drug Resistant Epilepsy / surgery
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Male
  • Nitriles
  • Patch-Clamp Techniques
  • Pyridones / pharmacology*
  • Receptors, AMPA / antagonists & inhibitors*
  • Synaptic Potentials / drug effects*

Substances

  • Anticonvulsants
  • Decanoic Acids
  • Nitriles
  • Pyridones
  • Receptors, AMPA
  • decanoic acid
  • perampanel

Grants and funding

This work was funded by Epilepsy Research UK grant F1301; Birmingham Children's Hospital Research Fund (BCHRF) grant .