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

Autor: 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
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Annals of Clinical and Translational Neurology, Vol 7, Iss 6, Pp 883-890 (2020)
Druh dokumentu: article
ISSN: 2328-9503
DOI: 10.1002/acn3.51030
Popis: 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.
Databáze: Directory of Open Access Journals
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