Evidence map›Paper›PMID 39843911›Full record

ArticleNature communications2025

Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39.

Zhongxiao Fu, Mallikarjunarao Ganesana, Philip Hwang, Xiao Tan, Melissa Marie Kinkaid, Yu-Yo Sun, Emily Bian, Aden Weybright, Hong-Ru Chen, Katia Sol-Church and 8 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Microglia Modulate Information Processing in the Mouse Barrel Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Adenosine in the Brain: Recent Progress on Detection, Function, and Translation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Zhongxiao FuDepartment of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA. zf3e@virginia.edu.ORCID http://orcid.org/0000-0002-8850-6991
Mallikarjunarao GanesanaDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.
Philip HwangNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0003-4381-6707
Xiao TanDepartment of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA.
Melissa Marie KinkaidDepartment of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA.
Yu-Yo SunInstitute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
Emily BianDepartment of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA.
Aden WeybrightDepartment of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA.
Hong-Ru ChenDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.ORCID http://orcid.org/0000-0001-9016-2190
Katia Sol-ChurchDepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Ukpong B EyoDepartment of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-1294-475X
Clare PridansCentre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0001-9423-557X
Francisco J QuintanaAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8156-0736
Simon C RobsonDepartments of Anesthesia and Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6374-0194
Pankaj KumarDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0002-8702-8879
B Jill VentonDepartment of Chemistry, University of Virginia, Charlottesville, VA, USA.
Anne SchaeferNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-1051-3710
Chia-Yi KuanDepartment of Neuroscience, Center for Brain Immunology and Glia, University of Virginia School of Medicine, Charlottesville, VA, USA. alex.kuan@virginia.edu.ORCID http://orcid.org/0000-0002-3453-863X

Funding

Transcription Factors in Stimulant and Opioid ActionP01DA047233 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ERIC J. NESTLER · 2019 to 2026
$16.5M
Neuroprotective signaling and transcriptional pathways in microglia associated with Alzheimer's diseaseR01AG072489 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ALISON M GOATE, Anne Schaefer · 2022 to 2026
$6.3M
Multiplexed neurochemical methods to understand adenosine neuromodulationR01NS121014 · NINDS · UNIVERSITY OF VIRGINIA · PI B. JILL VENTON · 2022 to 2026
$3.0M
Age-dependent activation of microglia inflammatory state and its epigenetic modulationRF1AG068558 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCHAEFER, ANNE, TARAKHOVSKY, ALEXANDER · 2020 to 2020
$3.0M
Influence of T cell genotype/phenotype in atherosclerotic cardiovascular diseaseR01HL167511 · NHLBI · OHIO STATE UNIVERSITY · PI Richard J Gumina · 2023 to 2026
$2.9M
CMRO2 and Uncoupling of Oxidative-Phosphorylation in Experimental HIER01NS125677 · NINDS · UNIVERSITY OF VIRGINIA · PI Song Hu, Chia-Yi Kuan · 2022 to 2026
$2.8M
Treating neurotoxicity and cognitive deficits due to hyperphosphorylated tau.R01NS135693 · NINDS · UNIVERSITY OF VIRGINIA · PI Chia-Yi Kuan, Min-Hao Kuo · 2023 to 2026
$2.4M
Creatine Transporter Deficiency and Brain EnergeticsR01NS108763 · NINDS · UNIVERSITY OF VIRGINIA · PI KUAN, CHIA-YI · 2018 to 2022
$2.3M
Neutrophils and Monocytes in Pediatric Ischemic StrokeR01NS125788 · NINDS · UNIVERSITY OF VIRGINIA · PI Chia-Yi Kuan · 2022 to 2026
$2.1M
Microglia mediated suppression of dopamine induced neuronal responses and behaviorR01MH118329 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCHAEFER, ANNE · 2019 to 2023
$2.1M
Transcriptional control of microglia diversification and inflammationRF1NS106721 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Anne Schaefer, Alexander Tarakhovsky · 2026 to 2026
$2.0M
Transcriptional Control of Microglia Diversification and InflammationR01NS106721 · NINDS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SCHAEFER, ANNE, TARAKHOVSKY, ALEXANDER · 2020 to 2024
$2.0M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) NS125677Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) NS125788Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) NS127392NHLBI NIH HHS R01 HL094400NHLBI NIH HHS R01 HL167511NIA NIH HHS F31 AG074652NIA NIH HHS R01 AG068558NIA NIH HHS R01 AG072489NIA NIH HHS R21 AG065923NIA NIH HHS RF1 AG068558NICHD NIH HHS R21 HD109025NIDA NIH HHS P01 DA047233NIMH NIH HHS R01 MH118329NINDS NIH HHS R01 NS106721NINDS NIH HHS R01 NS108763NINDS NIH HHS R01 NS121014NINDS NIH HHS R01 NS125677NINDS NIH HHS R01 NS125788NINDS NIH HHS R01 NS135693NINDS NIH HHS R21 NS127392NINDS NIH HHS RF1 NS106721
6 · The paper itself

Abstract

Microglia and the border-associated macrophages contribute to the modulation of cerebral blood flow, but the mechanisms have remained uncertain. Here, we show that microglia regulate the cerebral blood flow baseline and the responses to whisker stimulation or intra-cisternal magna injection of adenosine triphosphate, but not intra-cisternal magna injection of adenosine in mice model. Notably, microglia repopulation corrects these cerebral blood flow anomalies. The microglial-dependent regulation of cerebral blood flow requires the adenosine triphosphate-sensing P2RY12 receptor and ectonucleotidase CD39 that initiates the dephosphorylation of extracellular adenosine triphosphate into adenosine in both male and female mice. Pharmacological inhibition or CX3CR1-CreER-mediated deletion of CD39 mimics the cerebral blood flow anomalies in microglia-deficient mice and reduces the upsurges of extracellular adenosine following whisker stimulation. Together, these results suggest that the microglial CD39-initiated breakdown of extracellular adenosine triphosphate co-transmitter is an important step in neurovascular coupling and the regulation of cerebrovascular reactivity.

Indexed as

Antigens, CDApyraseCerebrovascular CirculationMicrogliaAdenosineAdenosine TriphosphateAnimalsCX3C Chemokine Receptor 1FemaleMaleMiceMice, Inbred C57BLMice, KnockoutNeurovascular CouplingReceptors, Purinergic P2Y12VibrissaeAdenosineAdenosine TriphosphateAntigens, CDApyraseCD39 antigenCX3C Chemokine Receptor 1Cx3cr1 protein, mouseP2ry12 protein, mouseReceptors, Purinergic P2Y12

Identifiers

PMID39843911
PMCPMC11754601

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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.