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

Autor: Sunny Philip, Shakti Agrawal, Stuart D. Greenhill, Sukhvir Wright, William B. Lo, Richard A. Walsh, Nilesh Mundil, Max A Wilson, Gavin L. Woodhall, Stefano Seri
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Drug Resistant Epilepsy
Patch-Clamp Techniques
Adolescent
Pyridones
medicine.medical_treatment
Neurosciences. Biological psychiatry. Neuropsychiatry
AMPA receptor
Pharmacology
03 medical and health sciences
chemistry.chemical_compound
Perampanel
0302 clinical medicine
Nitriles
medicine
Humans
Receptors
AMPA
RC346-429
Child
Receptor
Research Articles
Epilepsy
business.industry
musculoskeletal
neural
and ocular physiology
General Neuroscience
Antagonist
Brain
Decanoic acid
Human brain
Synaptic Potentials
030104 developmental biology
medicine.anatomical_structure
Anticonvulsant
nervous system
chemistry
Child
Preschool
Anticonvulsants
Female
Neurology. Diseases of the nervous system
Neurology (clinical)
business
Decanoic Acids
030217 neurology & neurosurgery
RC321-571
Research Article
Ketogenic diet
Zdroj: Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology, Vol 7, Iss 6, Pp 883-890 (2020)
ISSN: 2328-9503
DOI: 10.1002/acn3.51030
Popis: 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: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje