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Citations to this article

A ketogenic diet suppresses seizures in mice through adenosine A1 receptors
Susan A. Masino, … , Eleonora Aronica, Detlev Boison
Susan A. Masino, … , Eleonora Aronica, Detlev Boison
Published June 23, 2011
Citation Information: J Clin Invest. 2011;121(7):2679-2683. https://doi.org/10.1172/JCI57813.
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A ketogenic diet suppresses seizures in mice through adenosine A1 receptors

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Abstract

A ketogenic diet (KD) is a high-fat, low-carbohydrate metabolic regimen; its effectiveness in the treatment of refractory epilepsy suggests that the mechanisms underlying its anticonvulsive effects differ from those targeted by conventional antiepileptic drugs. Recently, KD and analogous metabolic strategies have shown therapeutic promise in other neurologic disorders, such as reducing brain injury, pain, and inflammation. Here, we have shown that KD can reduce seizures in mice by increasing activation of adenosine A1 receptors (A1Rs). When transgenic mice with spontaneous seizures caused by deficiency in adenosine metabolism or signaling were fed KD, seizures were nearly abolished if mice had intact A1Rs, were reduced if mice expressed reduced A1Rs, and were unaltered if mice lacked A1Rs. Seizures were restored by injecting either glucose (metabolic reversal) or an A1R antagonist (pharmacologic reversal). Western blot analysis demonstrated that the KD reduced adenosine kinase, the major adenosine-metabolizing enzyme. Importantly, hippocampal tissue resected from patients with medically intractable epilepsy demonstrated increased adenosine kinase. We therefore conclude that adenosine deficiency may be relevant to human epilepsy and that KD can reduce seizures by increasing A1R-mediated inhibition.

Authors

Susan A. Masino, Tianfu Li, Panos Theofilas, Ursula S. Sandau, David N. Ruskin, Bertil B. Fredholm, Jonathan D. Geiger, Eleonora Aronica, Detlev Boison

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 Total
Citations: 6 10 11 10 20 15 15 9 13 8 7 12 11 16 9 172
Citation information
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Citations to this article in year 2017 (13)

Title and authors Publication Year
Epilepsy and astrocyte energy metabolism
D Boison, C Steinhäuser
Glia 2017
Commonalities in epileptogenic processes from different acute brain insults: Do they translate?
P Klein, R Dingledine, E Aronica, C Bernard, I Blümcke, D Boison, MJ Brodie, AR Brooks-Kayal, J Engel, PA Forcelli, LJ Hirsch, RM Kaminski, H Klitgaard, K Kobow, DH Lowenstein, PL Pearl, A Pitkänen, N Puhakka, MA Rogawski, D Schmidt, M Sillanpää, RS Sloviter, C Steinhäuser, A Vezzani, MC Walker, W Löscher
Epilepsia 2017
Novel therapeutic approaches for disease-modification of epileptogenesis for curing epilepsy
BL Clossen, DS Reddy
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2017
Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder
DN Ruskin, MI Murphy, SL Slade, SA Masino, G Chapouthier
PloS one 2017
New insights into the mechanisms of the ketogenic diet:
D Boison
Current Opinion in Neurology 2017
Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse
DN Ruskin, JA Fortin, SN Bisnauth, SA Masino
Physiology & Behavior 2017
Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments
ML Brownlow, SH Jung, RJ Moore, N Bechmann, R Jankord
Frontiers in molecular neuroscience 2017
Synergistic protection against acute flurothyl-induced seizures by adjuvant treatment of the ketogenic diet with the type 2 diabetes drug pioglitazone
TA Simeone, SA Matthews, KA Simeone
Epilepsia 2017
Adenosine A1 Receptor Antagonism Abolished the Anti-seizure Effects of Exogenous Ketone Supplementation in Wistar Albino Glaxo Rijswijk Rats
Z Kovács, DP DAgostino, A Dobolyi, C Ari
Frontiers in molecular neuroscience 2017
Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations
H Feng, B Sjögren, B Karaj, V Shaw, A Gezer, RR Neubig
Neurology 2017
Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?
M Elamin, DN Ruskin, SA Masino, P Sacchetti
Frontiers in molecular neuroscience 2017
Pathophysiological Role of Purines and Pyrimidines in Neurodevelopment: Unveiling New Pharmacological Approaches to Congenital Brain Diseases
M Fumagalli, D Lecca, MP Abbracchio, S Ceruti
Frontiers in pharmacology 2017
The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms
Y Zhang, J Xu, K Zhang, W Yang, B Li
Current neuropharmacology 2017

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