ArticleAnnals of neurology2015
Ketone bodies mediate antiseizure effects through mitochondrial permeability transition.
Article in Annals of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 185 citations in OpenAlex.
- Effects of ketogenic diet on health outcomes: an umbrella review of meta-analyses of randomized clinical trials.BMC medicine · 2023Pooled it
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- The value of targeting ketone body metabolism in inflammatory and autoimmune diseases.Journal of translational medicine · 2026Review
- Targeted Reduction of Excessive Mitochondrial Superoxide by Mitoquinone Rescues Cognitive Impairment Without Affecting Spontaneous Recurrent Seizures in a Mouse Model of Temporal Lobe Epilepsy.Antioxidants (Basel, Switzerland) · 2026Article
- Ketogenic Strategies in Neonatal Hypoxic-Ischemic Encephalopathy-The Road to Opening Up: A Scoping Review.Neurology international · 2026Review
- Ketogenic diet for infantile epileptic spasms.Epilepsia open · 2025Article
- Article
- Potential inflammatory mechanisms of the ketogenic diet against febrile infection-related epilepsy syndrome.Acta epileptologica · 2025Review
- Exposure to β-hydroxybutyrate reduces the operating set point and increases excitability in hippocampal circuitry of healthy mice.Frontiers in pharmacology · 2025Article
- Nutritional strategies in abdominal surgery: the potential of ketogenic diet.Frontiers in nutrition · 2025Review
- Acetoacetate, a ketone body, attenuates neuronal bursts in acutely-induced epileptiform slices of the mouse hippocampus.Frontiers in cellular neuroscience · 2025Article
- Ketogenic diet as a therapeutic approach in autism spectrum disorder: a narrative review.Metabolic brain disease · 2024Review
- Metabolic aspects of genetic ion channel epilepsies.Journal of neurochemistry · 2024Review
- Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice.Molecular metabolism · 2024Article
- Putative Role of Adenosine A1 Receptors in Exogenous Ketone Supplements-Evoked Anti-Epileptic Effect.International journal of molecular sciences · 2024Review
- NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development.International journal of molecular sciences · 2024Review
- Review
- Review
- Drug resistant epilepsy and ketogenic diet: A narrative review of mechanisms of action.World neurosurgery: X · 2024Review
- The role of mitochondrial uncoupling in the regulation of mitostasis after traumatic brain injury.Neurochemistry international · 2024Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveKetone bodies (KB) are products of fatty acid oxidation and serve as essential fuels during fasting or treatment with the high-fat antiseizure ketogenic diet (KD). Despite growing evidence that KB exert broad neuroprotective effects, their role in seizure control has not been firmly demonstrated. The major goal of this study was to demonstrate the direct antiseizure effects of KB and to identify an underlying target mechanism.
methodsWe studied the effects of both the KD and KB in spontaneously epileptic Kcna1-null mice using a combination of behavioral, planar multielectrode, and standard cellular electrophysiological techniques. Thresholds for mitochondrial permeability transition (mPT) were determined in acutely isolated brain mitochondria.
resultsKB alone were sufficient to: (1) exert antiseizure effects in Kcna1-null mice, (2) restore intrinsic impairment of hippocampal long-term potentiation and spatial learning-memory defects in Kcna1-null mutants, and (3) raise the threshold for calcium-induced mPT in acutely prepared mitochondria from hippocampi of Kcna1-null animals. Targeted deletion of the cyclophilin D subunit of the mPT complex abrogated the effects of KB on mPT, and in vivo pharmacological inhibition and activation of mPT were found to mirror and reverse, respectively, the antiseizure effects of the KD in Kcna1-null mice.
interpretationThe present data reveal the first direct link between mPT and seizure control, and provide a potential mechanistic explanation for the KD. Given that mPT is increasingly being implicated in diverse neurological disorders, our results suggest that metabolism-based treatments and/or metabolic substrates might represent a worthy paradigm for therapeutic development.
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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.