ArticleCNS neuroscience & therapeutics2015
Inhibition of G protein-coupled receptor 81 (GPR81) protects against ischemic brain injury.
Article in CNS neuroscience & therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Risk factors for neurological complications in adult ECMO patients: a systematic review and meta-analysis.Frontiers in medicine · 2025Pooled it
- Unveiling the "Glycolysis-Lactate-Lactylation" Axis: A Novel Target in Ischemic Cerebrovascular Disease.Neuroscience bulletin · 2026Review
- Metabolic Bottlenecks and Opportunities: Reshaping the Tumor Microenvironment for Cancer Immunotherapy.Cells · 2026Review
- Glycolysis drives vascular hyperpermeability in acute lung injury via lactate-GPR81 axis in endothelial cells.Cell communication and signaling : CCS · 2026Article
- Exogenous lactate administration alleviates post-cardiac arrest brain injury by coordinating metabolic reprogramming and pathological mitophagy suppression.Cellular and molecular life sciences : CMLS · 2026Article
- Lactate metabolism and lactylation: Therapeutic and pre-clinical implications in neovascularization in peripheral artery disease.Journal of pharmaceutical analysis · 2026Review
- Lactylation in colorectal cancer: Unveiling novel mechanisms in metabolism, progression and therapeutic targeting.Clinical and translational medicine · 2026Review
- The Lactate Nexus: A Molecular Bridge Linking Physical Activity, Sleep, and Cognitive Enhancement.Biomedicines · 2026Review
- HIIT-induced lactate/GPR81 signaling with dual branches converging on ERK1/2 contributes to hippocampal synaptic remodeling and memory improvement.Frontiers in cell and developmental biology · 2026Article
- The lactate shuttle in ageing: a metabolic bridge between muscle fatigue and brain resilience.Frontiers in physiology · 2026Review
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Functional and Mechanistic Insights of 3-Hydroxybutyrate (3-OBA) in Bladder Cancer.Molecules (Basel, Switzerland) · 2025Article
- A review of the link between the lactate-GPR81 axis and mitochondrial angiopathy in MELAS based on imaging characteristics.Journal of neurology · 2025Review
- Multifunctional hydrogel promotes rotator cuff healing through anti-inflammation and vascularization.Materials today. Bio · 2025Article
- Lactate Metabolism and Lactylation Modification: New Opportunities and Challenges in Cardiovascular Disease.MedComm · 2025Review
- Metabolic Dysregulation in Parkinson's Disease: Non-Oxidative Phosphorylation and Its Role in Brain Energy Metabolism.Aging and disease · 2025Review
- Structures of G-protein coupled receptor HCAR1 in complex with Gi1 protein reveal the mechanistic basis for ligand recognition and agonist selectivity.PLoS biology · 2025Article
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- The impact of glycolysis on ischemic stroke: from molecular mechanisms to clinical applications.Frontiers in neurology · 2025Review
- The roles of lactate and the interplay with mCell biology and toxicology · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimLactates accumulate in ischemic brains. G protein-coupled receptor 81 (GPR81) is an endogenous receptor for lactate. We aimed to explore whether lactate is involved in ischemic injury via activating GPR81.
methodsN2A cells were transfected with GFP-GPR81 plasmids 24 h previously, and then treated with GPR81 antagonist 3-hydroxy-butyrate (3-OBA) alone or cotreated with agonists lactate or 3, 5-dihydroxybenzoic acid (3, 5-DHBA) during 3 h of oxygen-glucose deprivation (OGD). Adult male C57BL/6J mice and primary cultured cortical neurons were treated with 3-OBA at the onset of middle cerebral artery occlusion (MCAO) or OGD, respectively.
resultsThe GPR81 overexpression increased the cell vulnerability to ischemic injury. And GPR81 antagonism by 3-OBA significantly prevented cell death and brain injury after OGD and MCAO, respectively. Furthermore, inhibition of GPR81 reversed ischemia-induced apoptosis and extracellular signal-regulated kinase (ERK) signaling may be involved in the neuroprotection.
conclusionsG protein-coupled receptor 81 (GPR81) inhibition attenuated ischemic neuronal death. Lactate may aggravate ischemic brain injury by activating GPR81. GPR81 antagonism might be a novel therapeutic strategy for the treatment of cerebral ischemia.
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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.