ArticleNeuropharmacology2015
Ketogenic diet prevents epileptogenesis and disease progression in adult mice and rats.
Article in Neuropharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 154 citations in OpenAlex.
- Therapeutic Potential Target of Adenosine for Epilepsy: Focusing on Its Interaction with the Molecular Epileptogenic Network.Biomolecules · 2026Review
- Ketone bodies in kidney diseases: novel insights.Frontiers in immunology · 2026Review
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- Vagus Nerve Stimulation Inhibits DNA and RNA Methylation in a Rat Model of Pilocarpine-Induced Temporal Lobe Epilepsy.CNS neuroscience & therapeutics · 2025Article
- High Fat Low Carbohydrate Diet Is Linked to CNS Autoimmunity Protection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Adenosine Kinase: An Epigenetic Modulator and Drug Target.Journal of inherited metabolic disease · 2025Review
- VDAC1 Inhibition Mitigates Inflammatory Status and Oxidative Stress in Epileptic Mice Treated with the Ketogenic Diet.Neurochemical research · 2025Article
- Ketogenic diet, adenosine, and dopamine in addiction and psychiatry.Frontiers in nutrition · 2025Review
- Neuroglia and brain energy metabolism.Handbook of clinical neurology · 2025Review
- Pharmacological inhibition of ENT1 enhances the impact of specific dietary fats on energy metabolism gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Brain energy metabolism: A roadmap for future research.Journal of neurochemistry · 2024Review
- Underlying mechanisms of ketotherapy in heart failure: current evidence for clinical implementations.Frontiers in pharmacology · 2024Review
- Low glycemic index diet restrains epileptogenesis in a gender-specific fashion.Cellular and molecular life sciences : CMLS · 2023Article
- Review
- Astrocyte-neuron circuits in epilepsy.Neurobiology of disease · 2023Review
- Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder.International journal of molecular sciences · 2023Review
- Emerging Molecular Targets for Anti-Epileptogenic and Epilepsy Modifying Drugs.International journal of molecular sciences · 2023Review
- Current knowledges in pharmaconutrition: "Frontiers in nutrition · 2023Review
- Assessing the association between supplemented puppyhood dietary fat sources and owner-reported epilepsy in adulthood, among Finnish companion dogs.Frontiers in veterinary science · 2023Article
- Astrocytes in the initiation and progression of epilepsy.Nature reviews. Neurology · 2022Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.