Abolishing spontaneous epileptiform activity in human brain tissue through AMPA receptor inhibition.
Adolescent
Anticonvulsants
/ pharmacology
Brain
/ drug effects
Child
Child, Preschool
Decanoic Acids
/ pharmacology
Drug Resistant Epilepsy
/ drug therapy
Epilepsy
/ drug therapy
Female
Humans
Male
Nitriles
Patch-Clamp Techniques
Pyridones
/ pharmacology
Receptors, AMPA
/ antagonists & inhibitors
Synaptic Potentials
/ drug effects
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
10
01
2020
revised:
04
03
2020
accepted:
05
03
2020
pubmed:
20
5
2020
medline:
20
4
2021
entrez:
20
5
2020
Statut:
ppublish
Résumé
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. Using brain tissue resected from children with intractable epilepsy, we recorded the effects of PER and DEC in vitro. 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. This study confirms AMPAR antagonists inhibit epileptiform discharges in brain tissue resected in a wide range of pediatric epilepsies.
Identifiants
pubmed: 32426918
doi: 10.1002/acn3.51030
pmc: PMC7318092
doi:
Substances chimiques
Anticonvulsants
0
Decanoic Acids
0
Nitriles
0
Pyridones
0
Receptors, AMPA
0
decanoic acid
4G9EDB6V73
perampanel
H821664NPK
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
883-890Informations de copyright
© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Ann Neurol. 2015 Mar;77(3):381-98
pubmed: 25369168
Nature. 2019 Sep;573(7772):61-68
pubmed: 31435019
Ann Neurol. 1999 Dec;46(6):816-26
pubmed: 10589533
Neuropharmacology. 2009 Sep;57(4):356-68
pubmed: 19616018
Sci Rep. 2018 Mar 7;8(1):4158
pubmed: 29515159
J Neurol Sci. 1996 Dec;144(1-2):119-27
pubmed: 8994113
Handb Clin Neurol. 2018;150:319-333
pubmed: 29496151
Arch Dis Child. 1986 Dec;61(12):1173-7
pubmed: 3492967
J Neurosci Methods. 2006 Jul 15;155(1):1-19
pubmed: 16753220
Epilepsia. 2018 Nov;59(11):e172-e178
pubmed: 30324610
J Pharmacol Exp Ther. 2014 Oct;351(1):124-33
pubmed: 25027316
Acta Neurol Scand Suppl. 2013;(197):9-18
pubmed: 23480151
Lancet Neurol. 2018 Jan;17(1):84-93
pubmed: 29263011
Ann Neurol. 2009 Apr;65(4):424-34
pubmed: 19338055
Brain. 2016 Feb;139(Pt 2):431-43
pubmed: 26608744
Neuropharmacology. 2019 Nov 1;158:107728
pubmed: 31356824
J Neurosci Methods. 2016 Feb 15;260:221-32
pubmed: 26434706
Clin Chem. 1982 Apr;28(4 Pt 1):642-5
pubmed: 7074833
Brain. 2004 Jul;127(Pt 7):1626-40
pubmed: 15175227
Epilepsia. 2017 Oct;58(10):1686-1696
pubmed: 28755452
Neuron. 2018 Dec 5;100(5):1194-1208.e5
pubmed: 30392798
J Neurosci. 2007 Sep 12;27(37):9866-73
pubmed: 17855601