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Purinergic receptor P2RY12-dependent microglial closure of the injured blood–brain barrier
Open accessAbstract
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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“Although initially considered 'quiescent' cells primarily responsible for clearing cellular debris in the brain, microglia are now known as dynamic players in synaptic pruning, maintaining homeostasis and are primary responders to insult and injury in the CNS (Lou et al, 2016;Nimmerjahn et al, 2005;Paolicelli et al, 2011).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Lou et al, 2016
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“In this model, focal cerebrovascular damage resulted in a rapid, purinergic receptor–dependent projection of microglia processes that walled off the damaged vessel, limiting the extent of BBB leakage (134).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [134]
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Metadata
- 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)
- 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
- 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
- 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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