The AMPA receptor antagonist perampanel suppresses epileptic activity in human focal cortical dysplasia

Abstract

Focal cortical dysplasia (FCD) is one of the most common malformations causing refractory epilepsy. Dysregulation of glutamatergic systems plays a critical role in the hyperexcitability of dysplastic neurons in FCD lesions. The pharmacoresistant nature of epilepsy associated with FCD may be due to a lack of well tolerated and precise antiepileptic drugs that can target glutamate receptors. Here, for the first time in human FCD brain slices, we show that the established, non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, perampanel has potent antiepileptic action. Moreover, we demonstrate that this effect is due to a reduction in burst firing behavior in human FCD microcircuits. These data support a potential role for the treatment of refractory epilepsy associated with FCD in human patients.

Publication DOI: https://doi.org/10.1002/epi4.12549
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
College of Health & Life Sciences
College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Clinical and Systems Neuroscience
Additional Information: © 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy 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: This work has been supported by investigator-initiated grants from Eisai (MOC and GLW), Birmingham Children’s Hospital Charities grant BCHRF349 (SS, GLW) and Aston Brain Centre (GLW), the Wellcome Trust/EPSRC (102037; RGW and MOC), and a CAPES-funded (Brazil) PhD studentship (BEX-0437-14-0; ABDS, RGW, and MOC).
Uncontrolled Keywords: Epilepsy,focal cortical dysplasia,glutamate,perampanel,AMPA
Publication ISSN: 2470-9239
Last Modified: 16 Feb 2024 18:51
Date Deposited: 19 Oct 2021 08:00
Full Text Link:
Related URLs: https://onlinel ... 1002/epi4.12549 (Publisher URL)
PURE Output Type: Article
Published Date: 2021-10-15
Published Online Date: 2021-10-15
Accepted Date: 2021-10-15
Authors: Brito Da Silva, Anderson
Pennifold, Jane
Henley, Ben
Chatterjee, Koustav
Bateman, David
Whittaker, Roger W.
Joshi, Abhijit
Kumar, Hrishikesh
Nicholson, Claire
Baker, Mark R.
Greenhill, Stuart D. (ORCID Profile 0000-0002-5038-5258)
Walsh, Richard
Seri, Stefano (ORCID Profile 0000-0002-9247-8102)
Jones, Roland S.g.
Woodhall, Gavin L. (ORCID Profile 0000-0003-1281-9008)
Cunningham, Mark O.

Download

[img]

Version: Accepted Version

Access Restriction: Restricted to Repository staff only

License: Creative Commons Attribution


[img]

Version: Published Version

License: Creative Commons Attribution

| Preview

Export / Share Citation


Statistics

Additional statistics for this record