ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2022
Neuronal GPR81 regulates developmental brain angiogenesis and promotes brain recovery after a hypoxic ischemic insult.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Lactate alleviates early brain damage after subarachnoid hemorrhage: Regulation of lipid metabolism.Neural regeneration research · 2026Article
- Early GPR81/MCT1 rise and late lactate-NAD(H) Build-up in an LPS model of PD.Metabolic brain disease · 2026Article
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- Histone lactylation modification and its role in cerebral ischemia-reperfusion injury (Review).Biomedical reports · 2026Review
- Lactate receptor HCAR1 in neonatal hypoxic-ischemic seizures.Epilepsia · 2026Article
- Lactate: elucidating its indispensable role in human health.Molecular cancer · 2026Review
- Lactate, a Spearhead of Cancer Aggressiveness: Metabolic Reprogramming, Immune Suppression, and Metastatic Progression.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Review
- Lactate promotes mitochondrial biogenesis and fusion via GPR81 to enhance synaptic plasticity-related protein expression in hippocampal cells.Frontiers in cell and developmental biology · 2026Article
- 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
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Lactylation in ischemic brain injury-metabolic mechanisms, neuroinflammation, and therapeutic targets: A review.Biomolecules & biomedicine · 2025Review
- A review of the link between the lactate-GPR81 axis and mitochondrial angiopathy in MELAS based on imaging characteristics.Journal of neurology · 2025Review
- Article
- 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
- Balancing Anti-Inflammation and Neurorepair: The Role of Mineralocorticoid Receptor in Regulating Microglial Phenotype Switching After Traumatic Brain Injury.CNS neuroscience & therapeutics · 2025Article
- Lactylation in Tumor Immune Escape and Immunotherapy: Multifaceted Functions and Therapeutic Strategies.Research (Washington, D.C.) · 2025Review
- Endoplasmic Reticulum Stress Delays Choroid Development in the HCAR1 Knockout Mouse.The American journal of pathology · 2024Article
- Lactate Protects Microglia and Neurons from Oxygen-Glucose Deprivation/Reoxygenation.Neurochemical research · 2024Article
- Brain energy metabolism: A roadmap for future research.Journal of neurochemistry · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Perinatal hypoxic/ischemic (HI) brain injury is a major clinical problem with devastating neurodevelopmental outcomes in neonates. During HI brain injury, dysregulated factor production contributes to microvascular impairment. Glycolysis-derived lactate accumulated during ischemia has been proposed to protect against ischemic injury, but its mechanism of action is poorly understood. Herein, we hypothesize that lactate via its G-protein coupled receptor (GPR81) controls postnatal brain angiogenesis and plays a protective role after HI injury. We show that GPR81 is predominantly expressed in neurons of the cerebral cortex and hippocampus. GPR81-null mice displayed a delay in cerebral microvascular development linked to reduced levels of various major angiogenic factors and augmented expression of anti-angiogenic Thrombospondin-1 (TSP-1) in comparison to their WT littermates. Coherently, lactate stimulation induced an increase in growth factors (VEGF, Ang1 and 2, PDGF) and reduced TSP-1 expression in neurons, which contributed to accelerating angiogenesis. HI injury in GPR81-null animals curtailed vascular density and consequently increased infarct size compared to changes seen in WT mice; conversely intracerebroventricular lactate injection increased vascular density and diminished infarct size in WT but not in GPR81-null mice. Collectively, we show that lactate acting via GPR81 participates in developmental brain angiogenesis, and attenuates HI injury by restoring compromised microvasculature.
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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.