Cited by 365Barrier Structure and Function StudiesNeuroinflammation and Neurodegeneration MechanismsTraumatic Brain Injury and Neurovascular Disturbances

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Purinergic receptor P2RY12-dependent microglial closure of the injured blood–brain barrier

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Lou, Nanhong, Takano, Takahiro, Pei, Yong, Xavier, Anna L., Goldman, Steven A., Nedergaard, Maiken·2016·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1520398113PMC PMC4743790

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Abstract

Significance: Brain endothelial cells, pericytes, and astrocytes participate in maintenance of the blood–brain barrier (BBB). Juxtavascular microglial cells are also an integral part of the neurovascular unit. We show here that, in response to capillary injury, microglial processes rapidly form a dense plexiform aggregate at the site of injury. Photoablation of microglial cells abolished closure of BBB leakage, whereas inhibition of P2RY12 (purinergic receptor P2Y, G-protein coupled, 12) receptors suppressed microglial process motility and prolonged BBB closure. Thus, microglial cells mediate rapid resealing of injury-induced leaks in BBB. These observations may have clinical importance as P2RY12 receptor antagonists are widely used as platelet inhibitors in patients with coronary artery and cerebrovascular disease at risk for stroke and its attendant disruption of the injured BBB.

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Additional file 3 of The Alzheimer’s disease-associated protective Plcγ2-P522R variant promotes immune functions
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Additional file 7 of Spatio-temporal dynamics of microglia phenotype in human and murine cSVD: impact of acute and chronic hypertensive states
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Additional file 6 of Spatio-temporal dynamics of microglia phenotype in human and murine cSVD: impact of acute and chronic hypertensive states
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Additional file 5 of Spatio-temporal dynamics of microglia phenotype in human and murine cSVD: impact of acute and chronic hypertensive states
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Qian, Y., Lai, L., Zhang, Y., Meng, Y., Song, Z., Huang, B., Song, G., Bo, S., & Yang, W. (2026) · Advanced Science · doi:10.1002/advs.78004
“P2RY12 is a purinergic receptor [ 34 ].”
Unilateral gene expression via maternally controlled zygotic recombination in DrosophilaPreprint
Currier, T. A., Tadres, D., Troper, J. E., Wang, Y., & Clandinin, T. R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.14.759140

Authors: Lou, N., Takano, T., Pei, Y., Xavier, A. L., Goldman, S. A., & Nedergaard, M.
Affiliations: University of Rochester Medicine (US)
University of Copenhagen (DK)
ORCID: Takano, Takahiro
Xavier, Anna L.
Goldman, Steven A.
Nedergaard, Maiken
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2016-01-11
Volume: 113
Issue: 4
Pages: 1074-1079
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1520398113
PMC: PMC4743790
OpenAlex: W2234493563
Cited by: 364
References: 56
Citations by year: 2026: 31 · 2025: 31 · 2024: 50 · 2023: 53 · 2022: 59 · 2021: 26 · 2020: 40 · 2019: 24 · 2018: 23 · 2017: 20 · 2016: 6
FWCI: 13.33
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.pnas.org/preview_site/misc/userlicense.xhtml (vor, 182 d)
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
Funders: NIH/NIDCR (R01DE022743)
NIH/NINDS (R01NS075177)
NIH/NCCIH (R01AT007945)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords: P2Y12 receptor, microglia, blood-brain barrier integrity, microglial chemotaxis, neurovascular unit, cerebrovascular injury, clopidogrel, G protein-coupled receptors
MeSH terms: Clopidogrel, Animals, Blood-Brain Barrier, Cell Movement, Male, Mice, Inbred C57BL, Platelet Aggregation Inhibitors, Ticlopidine, Microglia, Mice, Receptors, Purinergic P2Y12

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Purinergic receptor P2RY12-dependent microglial closure of the injured blood–brain barrier

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