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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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“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]
In the citing paper
“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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“Microglial cells are another important partner of the NVU, also implicated in BBB integrity and homeostasis, continuously surveying their surrounding environment and rapidly repairing the BBB following acute vessel injury [8].”
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“This purinergic signaling pathway promotes microglianeuron interactions, which shape neuroplasticity and circuit-level function in various contexts [10, 12, 29, 36, 37].”
BackgroundThe spatial and temporal structure of neural activity across the fly brain
Schaffer, E. S., Mishra, N., Whiteway, M. R., Li, W., Vancura, M. B., Freedman, J., Patel, K. B., Voleti, V., Paninski, L., Hillman, E. M. C., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41261-2 · Cited by 53
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“More recently, MG has also been identified as an important intervenient cell type in BBB function (Lou et al., 2016).”
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Microglia Polarization: A Novel Target of Exosome for Stroke Treatment
Wan, T., Huang, Y., Gao, X., Wu, W., & Guo, W. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.842320 · Cited by 50
Microglia directly associate with pericytes in the central nervous system
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“…noxious stimuli including stroke (Jolivel et al., 2015), traumatic brain injury (Grossmann et al., 2002), systemic inflammation (Haruwaka et al., 2019), laser-induced vascular injury (Lou et al., 2016), and experimental autoimmune encephalomyelitis (Davalos et al., 2012; Joost et al., 2019).”
BackgroundConnexin Channels at the Glio-Vascular Interface: Gatekeepers of the Brain
Bock, M. D., Leybaert, L., & Giaume, C. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2313-x · Cited by 54
“It was recently shown that these juxtavascular microglial cells then form a honeycomb structure encapsulating the leakage site and resealing the BBB within ~40 min after laser injury [161].”
Backgroundm6A methylation: Critical roles in aging and neurological diseases
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“In addition, P2Y12 receptor-mediated chemotaxis of microglia processes is necessary for the rapid closure of the BBB after its rupture (Lou et al., 2016).”
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“Another protective role of microglia is reported by Lou et al., wherein these glial cells facilitate repairing the breached BBB through purinergic receptor-mediated process (Lou et al 2016).”
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“Recently, a number of studies have also implicated the role of microglia in contributing to BBB integrity (Lou et al., 2016; Taylor et al., 2018; Halder and Milner, 2019, 2020).”
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Soto, M. S., & Sibson, N. R. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00414 · Cited by 42
Microglia have a grip on brain microvasculature
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“Several studies were carried out, showing that blocking P2Y12 can be beneficial for the outcome of various inflammatory conditions, such as sepsis [11,12], asthma [13,14], rheumatoid arthritis [14–16], and neuroinflammation [17,18].”
BackgroundTaylor, S. L., Mehina, E. M. F., White, E. R., Reeson, P. L., Yongblah, K., Doyle, K. P., & Brown, C. E. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0734-18.2018 · Cited by 41
“…exacerbates secondary vessel leakage after microbleed Next, we wanted to assess what impact a reduced microglial response in diabetic mice would have on microvessel integrity and repair using secondary plasma leakage as an indicator of this process, as previously described (Lou et al., 2016).”
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Li, F., Xu, D., Hou, K., Gou, X., & Li, Y. (2020) · Journal of Thrombosis and Thrombolysis · doi:10.1007/s11239-020-02098-4 · Cited by 40
A Comparative Biology of Microglia Across Species
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“Similarly, in both the mouse (Lou et al., 2016) and the zebrafish (Liu et al.”
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Barkaway, A., Attwell, D., & Korte, N. (2022) · Neurophotonics · doi:10.1117/1.nph.9.3.031914 · Cited by 38
“Specifically, in a manner dependent on ADP-sensing P2Y12 receptors, microglia extend processes toward, and aggregate at, sites of vascular damage (as induced by laser injury) and seal the broken vessel using a mechanism dependent on E-cadherin.(295) In addition, microglia may also secrete trophic factors to encourage…”
BackgroundInfluentialLi, F., Gallego, J., Tirko, N. N., Greaser, J., Bashe, D., Patel, R., Shaker, E., Valkenburg, G. E. V., Alsubhi, A. S., Wellman, S. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49709-9 · Cited by 38
“Faster migration of microglia toward the implantation site suggests that LIPUS could promote microglia to facilitate the closure of the wounds caused by microelectrode implantation, thereby potentially mitigating further neuronal damage by reducing the in fi ltration of blood contents 98 .”
Movers and shakers: Microglial dynamics and modulation of neural networks
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“as injured tissue, damaged blood vessels, or exogenous ATP (Davalos et al., 2005; Lou et al., 2016; Nimmerjahn et al., 2005).”
BackgroundEpigenetics and stroke: role of DNA methylation and effect of aging on blood–brain barrier recovery
Phillips, C. M., Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V. (2023) · Fluids and Barriers of the CNS · doi:10.1186/s12987-023-00414-7 · Cited by 35
Inflammation-induced TRPV4 channels exacerbate blood–brain barrier dysfunction in multiple sclerosis
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“Comparable to other neuroinflammatory diseases, microglia within MS lesions express higher activation markers and less P2RY12, a homeostatic marker, which also has been implied in vessel-microglia communication [81–84].”
BackgroundMicroglia modulate the cerebrovascular reactivity through ectonucleotidase CD39
Fu, Z., Ganesana, M., Hwang, P. H., Tan, X., Kinkaid, M. M., Sun, Y., Bian, E. J., Weybright, A., Chen, H., Sol‐Church, K., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56093-5 · Cited by 41
“Microglia detect the extracellular ATP and ADP, mainly through the high-af fi nity P2Y12 receptor, and either repair or exacerbate the blood-brain-barrier (BBB) injury in a context-and severity-dependent manner 11,22,23 .”
The antidiabetic drug glibenclamide exerts direct retinal neuroprotection
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“This hypothesis is further supported by recent reports demonstrating the expression of the purinergic receptor P2ry12 to be essential to promote microglial-driven neuroprotection and to support neuronal functions by dynamic interactions with synapses, as well as the microglia-mediated maintenance of BBB integrity afte…”
ResultA novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling
Hasan, D., Shono, A., van Kalken, C. K., van der Spek, P. J., Krenning, E. P., & Kotani, T. (2021) · Purinergic Signalling · doi:10.1007/s11302-021-09814-6 · Cited by 35
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“Experiments with RAGE-KO mice were also conducted and revealed that mice lacking functional RAGE exhibit reduced BBB permeability in TBI and smaller lesions in stroke compared to WT littermates (Muhammad et al., 2008; Okuma et al., 2012).”
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“Microglial cells Induces movement of juxta-vascular microglial processes to close the injured blood-brain barrier (BBB) and microglial activation [203, 204] 103 Microglial cells Promotes migratory, inflammatory (TNF-αand IL-6 release) responses [205] 104”
BackgroundMicroglia-Centered Combinatorial Strategies Against Glioblastoma
Martins, T. A., Schmassmann, P., Shekarian, T., Boulay, J., Ritz, M., Zanganeh, S., Berg, J. V., & Hütter, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.571951 · Cited by 32
“Eventually, P2RY12 was identified as a MG-specific marker in the brain parenchyma and P2ry12 MG reporter mice were generated, allowing the study of P2RY12-mediated MG chemotaxis to the site of BBB injuries (79, 112) (Table 1).”
Melief, J., Orre, M., Bossers, K., van Eden, C. G., Schuurman, K. G., Mason, M. R. J., Verhaagen, J., Hamann, J., & Huitinga, I. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0705-7 · Cited by 27
Fast microglial activation after severe traumatic brain injuries
Lier, J., Ondruschka, B., Bechmann, I., & Dreßler, J. (2020) · International Journal of Legal Medicine · doi:10.1007/s00414-020-02308-x · Cited by 33
Genetic insights into immune mechanisms of Alzheimer’s and Parkinson’s disease
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Structure, Pharmacology and Roles in Physiology of the P2Y12 Receptor
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“In addition, microglial response to injury was shown to contribute to the timely restoration of blood-brain barrier (52).”
BackgroundJobling, A. I., Greferath, U., Dixon, M., Quiriconi, P., Eyar, B., van Koeverden, A. K., Mills, S. A., Vessey, K. A., Bui, B. V., & Fletcher, E. L. (2025) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2025.101349 · Cited by 31
“…have both been linked with inflammation, injury and pathology in the brain and retina, it remains to be fully determined whether these mechanisms are responsible for microglial neurovascular coupling within the heathy tissue (Chapman et al., 2000; Lou et al., 2016; Rodriguez et al., 2024a).”
Microglia in the Brain Tumor Microenvironment
Cole, A. P., Hoffmeyer, E., Chetty, S. L., Cruz, J. C., Hamrick, F. A., Youssef, O. A., Cheshier, S. H., & Mitra, S. S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-49270-0_11 · Cited by 30
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“Similarly, while microglia likely play a beneficial role in repair, at least initially (8, 11, 19, 20), over time, they may prolong brain injury or promote neuronal and vascular degeneration (21–24).”
BackgroundInfluentialMorton, L., Arndt, P., Garza, A. P., Henneicke, S., Mattern, H., Gonzalez, M., Dityatev, A. E., Yilmazer‐Hanke, D., Schreiber, S., & Dunay, I. R. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01672-0 · Cited by 28
“Recent evidence has shown that microglial response to capillary lesions depends on the P2Y12 purinergic receptor (P2Y12R) for BBB repair [76, 77].”
BackgroundWhy not Intravenous Thrombolysis in Patients with Recurrent Stroke within 3 Months?
Wu, C., Wu, D., Chen, J., Li, C., & Ji, X. (2018) · Aging and Disease · doi:10.14336/ad.2017.0406 · Cited by 28
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“Resealing of the BBB is criti‐ cally dependent upon the activation of microglia (Lou et al., 2016).”
BackgroundPrinciples for coding associative memories in a compact neural network
Pritz, C. O., Itskovits, E., Bokman, E., Ruach, R., Gritsenko, V., Nelken, T., Menasherof, M., Azulay, A., & Zaslaver, A. (2023) · eLife · doi:10.7554/elife.74434 · Cited by 24
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“P2RY12 is a marker for homeostatic microglia and is a chemotactic receptor guiding microglia to sites of injury for repair (Lou et al., 2016).”
Knopp, R. C., Banks, W. A., & Erickson, M. A. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102648 · Cited by 27
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“Similarly, pharmacological inhibition of microglial chemotaxis by systemic Clopidogrel (a P2Y12R inhibitor) administration results in microglial inability to promote repair after laser-induced BBB injury (Lou et al., 2016).”
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“Beneficial functions of inflammatory cells include phagocytosis of debris (18–20), provision of CNS barrier support (21, 22), and trophic support for tissue healing and repair (22–25).”
BackgroundMaurya, S. K., Gupta, S., & Mishra, R. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1072046 · Cited by 26
“, 2016) and P2ry12 serves as chemotactic receptors, guiding the microglial cell processes movement near to local sites of CNS injury (Lou et al., 2016).”
BackgroundMicroglia and macrophages in the neuro-glia-vascular unit: From identity to functions
Chen, S., Li, J., Meng, S., He, T., Shi, Z., Wang, C., Wang, Y., Cao, H., Huang, Y., Zhang, Y., et al. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106066 · Cited by 24
“Notably, in previous studies, microglia that reside in the perivascular space were described in several different terms such as ‘juxtavascular microglia’(Mondo et al., 2020; Lou et al., 2016), ‘capillary-associated microglia’(Bisht et al.”
Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo
Boghozian, R., Sharma, S., Narayana, K., Cheema, M. S., & Brown, C. E. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2302892120 · Cited by 24
“Local changes in blood flow (63), the release of purines from damaged cells next to the injury site (64), or fibrinogen from blood plasma, are established signals for stimulating microglial process chemotaxis toward injury (27, 31, 64).”
BackgroundAn integral blood–brain barrier in adulthood relies on microglia-derived PDGFB
Weng, Y., Chen, N., Zhang, R., He, J., Ding, X., Cheng, G., Bi, Q., Lu, Y., Shen, X. Z., Wan, S., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.11.023 · Cited by 25
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“Blocking purinergic receptors to antagonize early microglial responses has been associated with a higher incidence of damage in models of mTBI [ 81 , 97 ] .”
InfluentialApoptosis of Endothelial Cells Contributes to Brain Vessel Pruning of Zebrafish During Development
Zhang, Y., Xu, B., Chen, Q., Yan, Y., Du, J., & Du, X.-F. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00222 · Cited by 25
“, 2016), and the closure of injured blood-brain barrier (Lou et al., 2016).”
BackgroundTyagi, A., Mirita, C., Shah, I., Reddy, P. H., & Pugazhenthi, S. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.716616 · Cited by 25
The Interplay Between Brain Vascular Calcification and Microglia
Maheshwari, U., Huang, S., Sridhar, S., & Keller, A. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.848495 · Cited by 24
Immune regulation in neurovascular units after traumatic brain injury
Wang, Z., & Chen, G. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106060 · Cited by 24
Mason, H. D., Johnson, A. M., Mihelson, N., Mastorakos, P., & McGavern, D. B. (2021) · JCI Insight · doi:10.1172/jci.insight.149229 · Cited by 23
“149229 extent of leakage following cerebrovascular injury (24, 25).”
BackgroundYou, Y., Chen, Z., & Hu, W. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108606 · Cited by 25
Microglia contact cerebral vasculature through gaps between astrocyte endfeet
Morris, G. P., Foster, C. G., Sutherland, B. A., & Grubb, S. (2024) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x241280775 · Cited by 23
“…previously shown that microglia prevalence and/or morphology can become significantly altered in response to various CNS injuries including Alzheimer’s disease, 12 epilepsy, 63 laser-induced vessel injury, 64 stroke, 65 systemic inflammation, 16 traumatic brain injury 66 and diabetic retinopathy.”
Hsueh, S., Luo, W., Tweedie, D., Kim, D. S., Kim, Y. K., Hwang, I., Gil, J.-E., Han, B., Chiang, Y. H., Selman, W. R., et al. (2021) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.1c00042 · Cited by 22
Microglia as a Hub for Suicide Neuropathology: Future Investigation and Prevention Targets
de Andrade, E. G., Ibáñez, F. G., & Tremblay, M. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.839396 · Cited by 22
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Pan, D., Rong, X., Li, H., Deng, Z., Wang, J., Liu, X., He, L., Xu, Y., & Tang, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.788407 · Cited by 21
Liu, S., Li, D., Yu, T., Zhu, J., Semyachkina-Glushkovskaya, O. V., & Zhu, D. Y. (2023) · Communications Biology · doi:10.1038/s42003-023-05630-3 · Cited by 23
“P2RY12 is essential for the ability of microglia to respond to extracellular nucleotides released by brain tissue damage, and the lack of P2RY12 signi fi cantly delays the ability of microglia to respond to local brain tissue damage 46,47 .”
Stroke recovery and rehabilitation in 2016: a year in review of basic science and clinical science
Zheng, H., Cao, N., Yin, Y., & Feng, W. (2017) · Stroke and Vascular Neurology · doi:10.1136/svn-2017-000069 · Cited by 22
“Lou et al investigated how juxtavascular microglial cells help to amend injured BBB. 3 After they used 2-photon focused laser excitation to trigger capillary damage in small focal brain lesions, the authors found that the microglial cells in the perivascular region were attracted to the site of capillary lesions, wher…”
BackgroundBrain macrophages in vascular health and dysfunction
Bijnen, M., Sridhar, S., Keller, A., & Greter, M. (2024) · Trends in Immunology · doi:10.1016/j.it.2024.11.012 · Cited by 20
Ayana, R., Singh, S., & Pati, S. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00266 · Cited by 20
“P2RY12-mediated microglial cell activation contributes to the rapid closure of BBB small leaks, by aggregation of microglial cells at the injury site.”
BackgroundZhang, H., Sumbria, R. K., Chang, R., Sun, J., Cribbs, D. H., Holmes, T. C., Fisher, M., & Xu, X. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02932-5 · Cited by 20
“Once at the site of injury, microglia perform important functions including phagocytosis of invading pathogens and are also capable of sealing and repairing brain capillary lesions [43].”
BackgroundThe Dual Nature of Microglia in Alzheimer’s Disease: A Microglia-Neuron Crosstalk Perspective
Xie, Z., Meng, J., Wu, Z., Nakanishi, H., Hayashi, Y., Kong, W., Lan, F., Narengaowa, Yang, Q., Qing, H., et al. (2023) · The Neuroscientist · doi:10.1177/10738584211070273 · Cited by 19
Blood brain barrier as an interface for alcohol induced neurotoxicity during development
Siqueira, M., & Stipursky, J. (2022) · NeuroToxicology · doi:10.1016/j.neuro.2022.03.009 · Cited by 19
Purinergic signaling in the male reproductive tract
Belardin, L. B., Brochu, K., Légaré, C., Battistone, M. A., & Breton, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1049511 · Cited by 20
Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice
Paul, M., Paúl, J., Hinwood, M., Hood, R. J., Martin, K., Abdolhoseini, M., Johnson, S. J., Pollack, M. R. P., Nilsson, M., & Walker, F. R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411706 · Cited by 19
Update on the mechanism of microglia involvement in post-stroke cognitive impairment
Zeng, T., Liu, J., Zhang, W., Yu, Y., Ye, X., Huang, Q., Li, P., & Jiang, Q. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1366710 · Cited by 20
Microglia Contributes to BAF-312 Effects on Blood–Brain Barrier Stability
Spampinato, S. F., Costantino, G., Merlo, S., Canonico, P. L., & Sortino, M. A. (2022) · Biomolecules · doi:10.3390/biom12091174 · Cited by 19
“Microglia migration can be advantageous in the preservation of BBB functions in the early phases of inflammation [12], while impaired microglial motility—for example, that induced by the P2RY12 antagonist clopidogrel—can increase BBB injury [42].”
BackgroundLight field microscopy in biological imaging
Yi, C., Zhu, L., Li, D., & Fei, P. (2022) · Journal of Innovative Optical Health Sciences · doi:10.1142/s1793545822300178 · Cited by 18
Interactions between microglia and glioma in tumor microenvironment
Tao, J., Dong, Y. J., Shao, W., Zhou, D., Wang, Y., Hou, S., Deng, K., & Lin, N. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1236268 · Cited by 23
“And it has been proposed that the swift closure of the BBB is dependent on the P2RY12driven chemotactic response of microglia after BBB damage (130).”
BackgroundEchinatin protects from ischemic brain injury by attenuating NLRP3-related neuroinflammation
Sun, L., Chen, D., Zhao, C., Hu, Y., Xu, Y., Xia, S., Yang, H., Bao, X., Zhang, Z., Zhou, C., et al. (2024) · Neurochemistry International · doi:10.1016/j.neuint.2024.105676 · Cited by 18
Roles for Microglia in Cryptococcal Brain Dissemination in the Zebrafish Larva
Nielson, J. A., & Davis, J. M. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.04315-22 · Cited by 15
“Another implication of these findings is that resident microglia have at least three potential roles in cryptococcal pathogenesis: (i) supporting the integrity of the BBB itself, as has been demonstrated in other contexts (28, 32); (ii) restricting yeast growth within the CNS; and (iii) actively bringing yeast cells a…”
BackgroundMethodMAVS signaling shapes microglia responses to neurotropic virus infection
Gern, O. L., Pavlou, A., Mulenge, F., Busker, L. M., Ghita, L., Aringo, A., Costa, B., Spanier, J., Waltl, I., Stangel, M., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03258-6 · Cited by 15
“To differentiate between infiltrating myeloid cells and CNS-resident microglia, we used P2RY12 as a reliable and specific marker of microglia [35, 37–41].”
MethodNaffaa, M. M. (2025) · Exploration of neuroscience · doi:10.37349/en.2025.100676 · Cited by 20
Bendig, J., Frank, A. K., & Reichmann, H. (2024) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2023.36 · Cited by 15
Is Alzheimer disease a failure of mobilizing immune defense? Lessons from cognitively fit oldest-old
Katsel, P., & Haroutunian, V. H. (2019) · Phlebolymphology · doi:10.31887/dcns.2019.21.1/vharoutunian · Cited by 14
Dynamic changes in mitochondria support phenotypic flexibility of microglia
Espinoza, K., Schaler, A. W., Gray, D. T., Sass, A. R., Escobar, A., Moore, K., Yu, M. A., Chamorro, C. G., & Biase, L. M. D. (2025) · Nature Communications · doi:10.1038/s41467-025-66709-5 · Cited by 15
“In addition to homeostatic tissue surveillance, microglia exhibit rapid and robust cell process extension toward focal sites of CNS injury 49 – 51 .”
Cranial irradiation acutely and persistently impairs injury-induced microglial proliferation
Belcher, E. K., Sweet, T. B., Karaahmet, B., Dionisio-Santos, D. A., Owlett, L. D., Leffler, K. A., Janelsins, M. C., Williams, J. P., Olschowka, J. A., & O’Banion, M. K. (2020) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2020.100057 · Cited by 13
P2Y12 receptor gene polymorphisms are associated with epilepsy
Wang, Q., Shi, N.-R., Lv, P., Liu, J., Zhang, J., Deng, B.-L., Zuo, Y.-Q., Yang, J., Wang, X., Chen, X., et al. (2022) · Purinergic Signalling · doi:10.1007/s11302-022-09848-4 · Cited by 15
“The P2Y12 receptor is part of the metabotropic (P2Y) receptor family with exclusive expression in the microglia of the CNS [17,18], and it is essential for brain homeostasis including synaptic plasticity [19], vascular repair [20], and chemotaxis and motility of microglia [21,22].”
BackgroundMiller‐Rhodes, P., Li, H., Velagapudi, R., Chiang, W., Terrando, N., & Gelbard, H. A. (2022) · The FASEB Journal · doi:10.1096/fj.202200184rr · Cited by 12
“BECs relay systemic inflammatory signals to microglia via soluble factors [39, 40] and direct microglial contacts with BECs [41-44].”
BackgroundInfluentialBarbosa, M., Santos, M., de Sousa, N., Duarte-Silva, S., Vaz, A. R., Salgado, A. J., & Brites, D. (2022) · Biomedicines · doi:10.3390/biomedicines10092120 · Cited by 14
“WT + vehicle, Figure 8A and Supplementary Table S4), which may compromise microglial motility and migration [52].”
Background
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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