ArticleThe Journal of experimental medicine2022
Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 252 citations in OpenAlex.
- A systematic review of the causes and consequences of spreading depolarization in neuroinflammation; implications for neurovascular disorders.Journal of neuroinflammation · 2025Pooled it
- Heart failure-induced reprogramming of salt-evoked neurovascular coupling in the rat hypothalamus.The Journal of physiology · 2026Article
- Hypothalamic neurovascular and extracellular matrix remodeling: Cellular niche orchestration of immune-metabolic adaptation to nutritional stress.Reviews in endocrine & metabolic disorders · 2026Review
- Biomedical Materials and Fabrication Methods for Construction of In Vitro Neurovascular Unit Models.Materials (Basel, Switzerland) · 2026Review
- Activity-dependent protein synthesis in neurons requires microglial-metabolic coupling.Cell metabolism · 2026Article
- Glioma-Associated Microglia Augment Neuronal Hyper-Excitability in Glioma.Brain tumor research and treatment · 2026Review
- Friend or foe? Glial-vascular interactions in health and neurodegenerative disease.Pharmacological reviews · 2026Review
- Review
- Brain endothelial GαEBioMedicine · 2026Article
- ECgo: All-optical induction of single endothelial cell injury and capillary occlusion in the brain.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Vessel-associated microglia are differentially activated and distributed in relation to systemic infection and Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Article
- Microglial Plasticity in Vascular Dementia: Mechanisms and Therapeutic Reprogramming.International journal of molecular sciences · 2026Review
- Endothelial tPA-dependent recruitment of microglia to vessels protects the blood-brain barrier after stroke.Fluids and barriers of the CNS · 2026Article
- Microglial polarization in retinal neovascularization: Friend or foe?Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Microglia Modulate Information Processing in the Mouse Barrel Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Dissecting the aberrant vasculature of glioblastoma: mechanisms and therapeutic targets.Cancer metastasis reviews · 2026Review
- Obesity as a catalyst for neurodegeneration.Nature metabolism · 2026Review
- Capillary-Associated Microglia in Neurovascular Coupling: Localization, Mechanisms, and Disease Implications.Journal of neuroinflammation · 2026Review
- Adiponectin deficiency drives cerebrovascular dysfunction and synergizes with amyloid-β to exacerbate alzheimer's pathology.Alzheimer's research & therapy · 2026Article
- Exploring Exercise-Linked Neurovascular Unit Adaptations and Sema3G Pathway Involvement in Rats with Vascular Cognitive Impairment.Neurochemical research · 2026Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 6 institutions in 2 countries.
Funding
Abstract
Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with cells in the neurovascular unit that shape CBF in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in mice, which is reiterated by chemogenetically induced microglial dysfunction associated with impaired ATP sensitivity. Hypercapnia induces rapid microglial calcium changes, P2Y12R-mediated formation of perivascular phylopodia, and microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Microglial actions modulate vascular cyclic GMP levels but are partially independent of nitric oxide. Finally, microglial dysfunction markedly impairs P2Y12R-mediated cerebrovascular adaptation to common carotid artery occlusion resulting in hypoperfusion. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation, with broad implications for common neurological diseases.
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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.