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.
Original language | English |
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Journal | Epilepsia Open |
Early online date | 15 Oct 2021 |
DOIs | |
Publication status | E-pub ahead of print - 15 Oct 2021 |
Bibliographical note
© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against EpilepsyThis 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).
Keywords
- Epilepsy
- focal cortical dysplasia
- glutamate
- perampanel
- AMPA