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

Sukhvir K. Wright; Max A. Wilson; Richard Walsh; William B. Lo; Nilesh Mundil; Shakti Agrawal; Sunny Philip; Stefano Seri; Stuart D. Greenhill; Gavin L. Woodhall

doi:10.1002/acn3.51030

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

Sukhvir K. Wright, Max A. Wilson, Richard Walsh, William B. Lo, Nilesh Mundil, Shakti Agrawal, Sunny Philip, Stefano Seri, Stuart D. Greenhill, Gavin L. Woodhall^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	883-890
Number of pages	8
Journal	Annals of Clinical and Translational Neurology
Volume	7
Issue number	6
Early online date	19 May 2020
DOIs	https://doi.org/10.1002/acn3.51030
Publication status	Published - 1 Jun 2020

Bibliographical note

© 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)

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10.1002/acn3.51030Licence: CC BY 3.0

Abolishing spontaneous epileptiform activity in human brain tissue
© 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.
Final published version, 803 KBLicence: CC BY 3.0

Cite this

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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.",

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AU - Mundil, Nilesh

AU - Agrawal, Shakti

AU - Philip, Sunny

AU - Seri, Stefano

AU - Greenhill, Stuart D.

AU - Woodhall, Gavin L.

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N2 - 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.

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

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