ArticleMetabolites2022
Lactate Neuroprotection against Transient Ischemic Brain Injury in Mice Appears Independent of HCAR1 Activation.
Article in Metabolites, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- HCAR1-mediated lactate signaling modulates motor behavior and regulates spontaneous firing in Purkinje cells.iScience · 2026Article
- Lack of cortistatin drives neuroimmune and vascular dysfunction in brain ischemia.Journal of biomedical science · 2026Article
- Astrocytic Redox Homeostasis as a Metabolic Modulator of DNA Damage and Repair in the Ischemic Penumbra.Cells · 2026Review
- Time-dependent plasma metabolic shifts and mechanistic insights into systemic consequences of cerebral ischemia in middle-aged patients.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Metabolic-Epigenetic-Immune axis in Ischemic Stroke: Lactate-derived Lactylation as a Key Regulator.Metabolic brain disease · 2026Review
- Exploration of the Preventive and Therapeutic Effects of D-Lactate Administration in a Mouse MCAO Model.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Lactate promotes longevity through redox-driven lipid remodeling inbioRxiv : the preprint server for biology · 2025Article
- Extracellular lactate improves neurogenesis by modulating H3K9 lactylation and SnoN expression under hypoxic conditions.Stem cell research & therapy · 2025Article
- Tracking Hyperpolarized [1-NMR in biomedicine · 2025Article
- Lactylation of histone by BRD4 regulates astrocyte polarization after experimental subarachnoid hemorrhage.Journal of neuroinflammation · 2024Article
- Lactate Protects Microglia and Neurons from Oxygen-Glucose Deprivation/Reoxygenation.Neurochemical research · 2024Article
- Blood and Brain Metabolites after Cerebral Ischemia.International journal of molecular sciences · 2023Review
- Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion.Scientific reports · 2023Article
- Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion.Research square · 2023Article
- Lactate-Mediated Signaling in the Brain-An Update.Brain sciences · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Lactate can protect against damage caused by acute brain injuries both in rodents and in human patients. Besides its role as a metabolic support and alleged preferred neuronal fuel in stressful situations, an additional signaling mechanism mediated by the hydroxycarboxylic acid receptor 1 (HCAR1) was proposed to account for lactate's beneficial effects. However, the administration of HCAR1 agonists to mice subjected to middle cerebral artery occlusion (MCAO) at reperfusion did not appear to exert any relevant protective effect. To further evaluate the involvement of HCAR1 in the protection against ischemic damage, we looked at the effect of HCAR1 absence. We subjected wild-type and HCAR1 KO mice to transient MCAO followed by treatment with either vehicle or lactate. In the absence of HCAR1, the ischemic damage inflicted by MCAO was less pronounced, with smaller lesions and a better behavioral outcome than in wild-type mice. The lower susceptibility of HCAR1 KO mice to ischemic injury suggests that lactate-mediated protection is not achieved or enhanced by HCAR1 activation, but rather attributable to its metabolic effects or related to other signaling pathways. Additionally, in light of these results, we would disregard HCAR1 activation as an interesting therapeutic strategy for stroke patients.
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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 Socratic graph.