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

Sukhvir K Wright1,2, Max A Wilson1, Richard Walsh3

  • 1Aston Neuroscience Institute, School of Life and Health Sciences, Aston University, Birmingham, UK.

Annals of Clinical and Translational Neurology
|May 20, 2020
PubMed

Insights

Decanoic acid (DEC) and perampanel (PER) inhibit epileptic activity in pediatric epilepsy tissue. Both compounds target amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), offering potential therapeutic strategies.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • The amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a key target for treating drug-refractory pediatric epilepsy.
  • Perampanel (PER) is an AMPAR antagonist, and decanoic acid (DEC), found in ketogenic diets, has shown pre-clinical anticonvulsant effects mediated by AMPARs.

Purpose of the Study:

  • To investigate the in vitro effects of PER and DEC on brain tissue resected from children with intractable epilepsy.
  • To assess the potential of AMPAR antagonism as a therapeutic strategy for pediatric epilepsy.

Main Methods:

  • Utilized brain tissue resected from pediatric epilepsy patients.
  • Performed in vitro recordings of local field potentials and excitatory synaptic transmission.
  • Administered PER and DEC to assess their effects on epileptiform activity.

Main Results:

  • Resected pediatric epilepsy tissue demonstrated spontaneous epileptic activity in vitro.
  • Both DEC and PER significantly inhibited epileptiform activity.
  • DEC and PER reduced excitatory synaptic transmission in the studied tissue.

Conclusions:

  • AMPAR antagonists, including DEC and PER, effectively inhibit epileptiform discharges in pediatric epilepsy.
  • These findings support the therapeutic potential of targeting AMPARs in a broad range of pediatric epilepsy conditions.
Abstract

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