ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Exploring the therapeutic efficacy and pharmacological mechanism of Guizhi Fuling Pill on ischemic stroke: a meta-analysis and network pharmacology analysis.Metabolic brain disease · 2024Pooled it
- Trial
- A Dose-Response Study on Human FGF21 to Inhibit Necrosis, Spectrin Breakdown, and to Increase Intracellular Cold Shock Proteins in Cultured Cortical Neurons Subjected to Oxygen-Glucose Deprivation Injury.Molecular neurobiology · 2026Article
- Lifestyles, metabolome and diabetic kidney disease: a cohort study.QJM : monthly journal of the Association of Physicians · 2026Article
- Inflammation-centered neurovascular-immune-metabolic remodeling in ischemic stroke: stage-dependent mechanisms, regulated cell death, and therapeutic translation.Frontiers in immunology · 2026Review
- Exercise-induced β-hydroxybutyrate contributes to cognitive improvement in aging mice.Journal of sport and health science · 2025Article
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Sirtuins Contribute to the Migraine-Stroke Connection.International journal of molecular sciences · 2025Review
- Intra-Arterial Deoxyribonuclease Therapy Improves Stroke Outcomes in Aged Mice.CNS neuroscience & therapeutics · 2025Article
- Targeting mitochondrial function as a potential therapeutic approach for allergic asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC.Frontiers in pharmacology · 2025Review
- Role of SIRT1 in Potentially Toxic Trace Elements (Lead, Fluoride, Aluminum and Cadmium) Associated Neurodevelopmental Toxicity.Biological trace element research · 2024Review
- Neuroregeneration Improved by Sodium-D,L-Beta-Hydroxybutyrate in Primary Neuronal Cultures.Pharmaceuticals (Basel, Switzerland) · 2024Article
- β-hydroxybutyrate and ischemic stroke: roles and mechanisms.Molecular brain · 2024Review
- Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice.Cell reports. Medicine · 2024Article
- Mitochondrial dysfunction: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2024Review
- Drug resistant epilepsy and ketogenic diet: A narrative review of mechanisms of action.World neurosurgery: X · 2024Review
- SIRT3 Activation a Promise in Drug Development? New Insights into SIRT3 Biology and Its Implications on the Drug Discovery Process.Journal of medicinal chemistry · 2024Review
- Article
- Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD(+)/NADH ratio. In this study, we investigated whether mitochondrial NAD(+)-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD(+)-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway.
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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.