The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
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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Nicoletti, I., Migliorati, G., Pagliacci, M. C., Grignani, F., & Riccardi, C. (1991) · Journal of Immunological Methods · doi:10.1016/0022-1759(91)90198-o · Cited by 4,562
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
Pathobiology of ischaemic stroke: an integrated view
Dirnagl, U., Iadecola, C., & Moskowitz, M. A. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(99)01401-0 · Cited by 3,943
ATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary Intervention
Steinhubl, S. R., Berger, P. B., Mann, J. T., Fry, E. T. A., DeLago, A. J., Wilmer, C. I., Topol, E. J., & for the CREDO Investigators (2002) · JAMA · doi:10.1001/jama.288.19.2411 · Cited by 3,071
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Microglia and macrophages in brain homeostasis and disease
Li, Q., & Barres, B. A. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.125 · Cited by 1,999
New tools for studying microglia in the mouse and human CNS
Bennett, M. L., Bennett, F. C., Liddelow, S. A., Ajami, B., Zamanian, J. L., Fernhoff, N. B., Mulinyawe, S. B., Bohlen, C. J., Adil, A., Tucker, A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1525528113 · Cited by 1,804
“Indeed, a recently published study suggests that P2ry12-mediated chemotaxis directly influences CNS hemostasis, a finding of great interest in the context of our transcriptomic data, and one that could inform future therapeutic interventions (57).”
BackgroundThe Microenvironmental Landscape of Brain Tumors
Quail, D. F., & Joyce, J. A. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.009 · Cited by 1,924
“Microglia can additionally contribute to regulating BBB integrity (da Fonseca et al., 2014) (Figure 2A), and specifically repair the BBB following injury in a purinergic receptor P2RY12-dependent manner (Lou et al., 2016).”
BackgroundBlood-brain barrier dysfunction and recovery after ischemic stroke
Jiang, X., Andjelkovic, A. V., Zhu, L., Yang, T., Bennett, M. V. L., Chen, J., Keep, R. F., & Shi, Y. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.10.001 · Cited by 967
Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.010 · Cited by 799
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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