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

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 DOI: https://doi.org/10.1002/acn3.51030
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences > Psychology
Life & Health Sciences
Life & Health Sciences > Clinical and Systems Neuroscience
Additional Information: © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding: Epilepsy Research UK. Grant Number: F1301 Birmingham Children's Hospital Research Fund (BCHRF)
Uncontrolled Keywords: Neuroscience(all),Clinical Neurology
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-06-01
Published Online Date: 2020-05-19
Accepted Date: 2020-03-05
Authors: Wright, Sukhvir K. ( 0000-0002-5464-3779)
Wilson, Max A.
Walsh, Richard
Lo, William B.
Mundil, Nilesh
Agrawal, Shakti
Philip, Sunny
Seri, Stefano ( 0000-0002-9247-8102)
Greenhill, Stuart D. ( 0000-0002-5038-5258)
Woodhall, Gavin L. ( 0000-0003-1281-9008)

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