Endothelial cells and macrophages as allies in the healthy and diseased brain.
Alzheimer’s disease
Angiogenesis
Antigen presentation
Endothelial cells
Microglia
Multiple sclerosis
Neuroinflammation
Perivascular macrophage
Stroke
Vascular remodelling
Journal
Acta neuropathologica
ISSN: 1432-0533
Titre abrégé: Acta Neuropathol
Pays: Germany
ID NLM: 0412041
Informations de publication
Date de publication:
12 Feb 2024
12 Feb 2024
Historique:
received:
30
10
2023
accepted:
20
01
2024
revised:
19
01
2024
medline:
13
2
2024
pubmed:
13
2
2024
entrez:
12
2
2024
Statut:
epublish
Résumé
Diseases of the central nervous system (CNS) are often associated with vascular disturbances or inflammation and frequently both. Consequently, endothelial cells and macrophages are key cellular players that mediate pathology in many CNS diseases. Macrophages in the brain consist of the CNS-associated macrophages (CAMs) [also referred to as border-associated macrophages (BAMs)] and microglia, both of which are close neighbours or even form direct contacts with endothelial cells in microvessels. Recent progress has revealed that different macrophage populations in the CNS and a subset of brain endothelial cells are derived from the same erythromyeloid progenitor cells. Macrophages and endothelial cells share several common features in their life cycle-from invasion into the CNS early during embryonic development and proliferation in the CNS, to their demise. In adults, microglia and CAMs have been implicated in regulating the patency and diameter of vessels, blood flow, the tightness of the blood-brain barrier, the removal of vascular calcification, and the life-time of brain endothelial cells. Conversely, CNS endothelial cells may affect the polarization and activation state of myeloid populations. The molecular mechanisms governing the pas de deux of brain macrophages and endothelial cells are beginning to be deciphered and will be reviewed here.
Identifiants
pubmed: 38347307
doi: 10.1007/s00401-024-02695-0
pii: 10.1007/s00401-024-02695-0
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
38Subventions
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 813294
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 813294
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 813294
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 813294
Organisme : H2020 Marie Skłodowska-Curie Actions
ID : 813294
Informations de copyright
© 2024. The Author(s).
Références
Alon T, Hemo I, Itin A, Pe’Er J, Stone J, Keshet E (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1:1024–1028. https://doi.org/10.1038/nm1095-1024
doi: 10.1038/nm1095-1024
pubmed: 7489357
Amann L, Masuda T, Prinz M (2023) Mechanisms of myeloid cell entry to the healthy and diseased central nervous system. Nat Immunol 24:393–407. https://doi.org/10.1038/s41590-022-01415-8
doi: 10.1038/s41590-022-01415-8
pubmed: 36759712
Aydin S, Pareja J, Schallenberg VM, Klopstein A, Gruber T, Page N et al (2023) Antigen recognition detains CD8(+) T cells at the blood-brain barrier and contributes to its breakdown. Nat Commun 14:3106. https://doi.org/10.1038/s41467-023-38703-2
doi: 10.1038/s41467-023-38703-2
pubmed: 37253744
pmcid: 10229608
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252. https://doi.org/10.1038/32588
doi: 10.1038/32588
pubmed: 9521319
Bartholomäus I, Kawakami N, Odoardi F, Schläger C, Miljkovic D, Ellwart JW et al (2009) Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462:94–98. https://doi.org/10.1038/nature08478
doi: 10.1038/nature08478
pubmed: 19829296
Becher B, Bechmann I, Greter M (2006) Antigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain. J Mol Med 84:532–543. https://doi.org/10.1007/s00109-006-0065-1
doi: 10.1007/s00109-006-0065-1
pubmed: 16773356
Bisht K, Okojie KA, Sharma K, Lentferink DH, Sun YY, Chen HR et al (2021) Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice. Nat Commun 12:5289. https://doi.org/10.1038/s41467-021-25590-8
doi: 10.1038/s41467-021-25590-8
pubmed: 34489419
pmcid: 8421455
Bonvento G, Bolaños JP (2021) Astrocyte-neuron metabolic cooperation shapes brain activity. Cell Metab 33:1546–1564. https://doi.org/10.1016/j.cmet.2021.07.006
doi: 10.1016/j.cmet.2021.07.006
pubmed: 34348099
Brown R, Benveniste H, Black SE, Charpak S, Dichgans M, Joutel A (2018) Understanding the role of the perivascular space in cerebral small vessel disease. Cardiovasc Res 114:1462–1473. https://doi.org/10.1093/cvr/cvy113
doi: 10.1093/cvr/cvy113
pubmed: 29726891
pmcid: 6455920
Bryant A, Li Z, Jayakumar R, Serrano-Pozo A, Woost B, Hu M et al (2023) Endothelial cells are heterogeneous in different brain regions and are dramatically altered in alzheimer’s disease. J Neurosci 43:4541–4557. https://doi.org/10.1523/JNEUROSCI.0237-23.2023
doi: 10.1523/JNEUROSCI.0237-23.2023
pubmed: 37208174
pmcid: 10278684
Cavanagh JB (1999) Corpora-amylacea and the family of polyglucosan diseases. Brain Res Rev 29:265–295. https://doi.org/10.1016/S0165-0173(99)00003-X
doi: 10.1016/S0165-0173(99)00003-X
pubmed: 10209236
Chang C-F, Goods BA, Askenase MH, Hammond MD, Renfroe SC, Steinschneider AF et al (2018) Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage. J Clin Investig 128:607–624. https://doi.org/10.1172/JCI95612
doi: 10.1172/JCI95612
pubmed: 29251628
Checchin D, Sennlaub F, Levavasseur E, Leduc M, Chemtob S (2006) Potential role of microglia in retinal blood vessel formation. Investigative Opthalmology & Visual Science 47:3595. https://doi.org/10.1167/iovs.05-1522
doi: 10.1167/iovs.05-1522
Chen AQ, Fang Z, Chen XL, Yang S, Zhou YF, Mao L et al (2019) Microglia-derived TNF-alpha mediates endothelial necroptosis aggravating blood brain-barrier disruption after ischemic stroke. Cell Death Dis 10:487. https://doi.org/10.1038/s41419-019-1716-9
doi: 10.1038/s41419-019-1716-9
pubmed: 31221990
pmcid: 6586814
Chen S, Tisch N, Kegel M, Yerbes R, Hermann R, Hudalla H et al (2017) CNS macrophages control neurovascular development via CD95L. Cell Rep 19:1378–1393. https://doi.org/10.1016/j.celrep.2017.04.056
doi: 10.1016/j.celrep.2017.04.056
pubmed: 28514658
Coupland K, Lendahl U, Karlström H (2018) Role of NOTCH3 mutations in the cerebral small vessel disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Stroke 49:2793–2800. https://doi.org/10.1161/strokeaha.118.021560
doi: 10.1161/strokeaha.118.021560
pubmed: 30355220
Csaszar E, Lenart N, Cserep C, Kornyei Z, Fekete R, Posfai B, et al (2022) Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions. J Exp Med 219: https://doi.org/10.1084/jem.20211071
Cserep C, Posfai B, Lenart N, Fekete R, Laszlo ZI, Lele Z et al (2020) Microglia monitor and protect neuronal function through specialized somatic purinergic junctions. Science 367:528–537. https://doi.org/10.1126/science.aax6752
doi: 10.1126/science.aax6752
pubmed: 31831638
D’Mello SR, Kindy MC (2020) Overdosing on iron: Elevated iron and degenerative brain disorders. Exp Biol Med 245:1444–1473. https://doi.org/10.1177/1535370220953065
doi: 10.1177/1535370220953065
Dalmau-Gasull A, Glavan M, Samawar SKR, Fumagalli S, Sorokin L, Vivien D et al (2023) Origin, function, and fate of CNS-associated macrophages in health and disease—an update. Submitted:
Davalos D, Ryu JK, Merlini M, Baeten KM, Le Moan N, Petersen MA, et al (2012) Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun 3: 1227 ARTN 1227 https://doi.org/10.1038/ncomms2230
Drieu A, Du S, Storck SE, Rustenhoven J, Papadopoulos Z, Dykstra T et al (2022) Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Nature 611:585–593. https://doi.org/10.1038/s41586-022-05397-3
doi: 10.1038/s41586-022-05397-3
pubmed: 36352225
pmcid: 9899827
Dudiki T, Meller J, Mahajan G, Liu H, Zhevlakova I, Stefl S et al (2020) Microglia control vascular architecture via a TGFbeta1 dependent paracrine mechanism linked to tissue mechanics. Nat Commun 11:986. https://doi.org/10.1038/s41467-020-14787-y
doi: 10.1038/s41467-020-14787-y
pubmed: 32080187
pmcid: 7033106
Dudvarski Stankovic N, Teodorczyk M, Ploen R, Zipp F, Schmidt MHH (2016) Microglia-blood vessel interactions: a double-edged sword in brain pathologies. Acta Neuropathol 131:347–363. https://doi.org/10.1007/s00401-015-1524-y
doi: 10.1007/s00401-015-1524-y
pubmed: 26711460
Dumas AA, Borst K, Prinz M (2021) Current tools to interrogate microglial biology. Neuron 109:2805–2819. https://doi.org/10.1016/j.neuron.2021.07.004
doi: 10.1016/j.neuron.2021.07.004
pubmed: 34390649
Dustin ML, Bromley SK, Kan Z, Peterson DA, Unanue ER (1997) Antigen receptor engagement delivers a stop signal to migrating T lymphocytes. Proc Natl Acad Sci U S A 94:3909–3913. https://doi.org/10.1073/pnas.94.8.3909
doi: 10.1073/pnas.94.8.3909
pubmed: 9108078
pmcid: 20541
Elmore MR, Najafi AR, Koike MA, Dagher NN, Spangenberg EE, Rice RA et al (2014) Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron 82:380–397. https://doi.org/10.1016/j.neuron.2014.02.040
doi: 10.1016/j.neuron.2014.02.040
pubmed: 24742461
pmcid: 4161285
Fain CE, Zheng J, Jin F, Ayasoufi K, Wu Y, Lilley MT, et al (2023) Discrete class I molecules on brain endothelium differentially regulate neuropathology in experimental cerebral malaria. Brain: https://doi.org/10.1093/brain/awad319
Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S et al (2010) Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood 116:829–840. https://doi.org/10.1182/blood-2009-12-257832
doi: 10.1182/blood-2009-12-257832
pubmed: 20404134
pmcid: 2938310
Faraco G, Park L, Anrather J, Iadecola C (2017) Brain perivascular macrophages: characterization and functional roles in health and disease. J Mol Med 95:1143–1152. https://doi.org/10.1007/s00109-017-1573-x
doi: 10.1007/s00109-017-1573-x
pubmed: 28782084
Faraco G, Sugiyama Y, Lane D, Garcia-Bonilla L, Chang H, Santisteban MM et al (2016) Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J Clin Invest 126:4674–4689. https://doi.org/10.1172/jci86950
doi: 10.1172/jci86950
pubmed: 27841763
pmcid: 5127678
Fernandez-Lopez D, Faustino J, Klibanov AL, Derugin N, Blanchard E, Simon F et al (2016) Microglial Cells Prevent Hemorrhage in Neonatal Focal Arterial Stroke. J Neurosci 36:2881–2893. https://doi.org/10.1523/JNEUROSCI.0140-15.2016
doi: 10.1523/JNEUROSCI.0140-15.2016
pubmed: 26961944
pmcid: 4783493
Fernando DA (1973) Myelin debris in cerebral blood capillaries. Acta Neuropathol 23:260–264. https://doi.org/10.1007/BF00687881
doi: 10.1007/BF00687881
pubmed: 4691832
Ford AL, Foulcher E, Lemckert FA, Sedgwick JD (1996) Microglia induce CD4 T lymphocyte final effector function and death. J Exp Med 184:1737–1745. https://doi.org/10.1084/jem.184.5.1737
doi: 10.1084/jem.184.5.1737
pubmed: 8920862
Forstreuter F, Lucius R, Mentlein R (2002) Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells. J Neuroimmunol 132:93–98. https://doi.org/10.1016/s0165-5728(02)00315-6
doi: 10.1016/s0165-5728(02)00315-6
pubmed: 12417438
Fournier AP, Tastet O, Charabati M, Hoornaert C, Bourbonniere L, Klement W, et al (2023) Single-Cell Transcriptomics Identifies Brain Endothelium Inflammatory Networks in Experimental Autoimmune Encephalomyelitis. Neurology(R) neuroimmunology & neuroinflammation 10: https://doi.org/10.1212/NXI.0000000000200046
Freria CM, Brennan FH, Sweet DR, Guan Z, Hall JC, Kigerl KA et al (2020) Serial systemic injections of endotoxin (LPS) elicit neuroprotective spinal cord microglia through IL-1-dependent cross talk with endothelial cells. J Neurosci 40:9103–9120. https://doi.org/10.1523/jneurosci.0131-20.2020
doi: 10.1523/jneurosci.0131-20.2020
pubmed: 33051350
pmcid: 7672996
Galea I, Bernardes-Silva M, Forse PA, van Rooijen N, Liblau RS, Perry VH (2007) An antigen-specific pathway for CD8 T cells across the blood-brain barrier. J Exp Med 204:2023–2030. https://doi.org/10.1084/jem.20070064
doi: 10.1084/jem.20070064
pubmed: 17682068
pmcid: 2118703
Garcia-Bonilla L, Shahanoor Z, Sciortino R, Nazarzoda O, Racchumi G, Iadecola C, Anrather J (2023) Brain and blood single-cell transcriptomics in acute and subacute phases after experimental stroke. bioRxiv: https://doi.org/10.1101/2023.03.31.535150
Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N (2015) Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol 78:887–900. https://doi.org/10.1002/ana.24512
doi: 10.1002/ana.24512
pubmed: 26312599
Goldstein JS, Chen T, Brunswick M, Mostowsky H, Kozlowski S (1998) Purified MHC class I and peptide complexes activate naive CD8+ T cells independently of the CD28/B7 and LFA-1/ICAM-1 costimulatory interactions. J Immunol 160:3180–3187
doi: 10.4049/jimmunol.160.7.3180
pubmed: 9531273
Gonzalez-Fierro C, Fonte C, Dufourd E, Cazaentre V, Aydin S, Engelhardt B, Caspi RR, Xu B, Martin-Blondel G, Spicer JAet al (2023) Effects of a Small-Molecule Perforin Inhibitor in a Mouse Model of CD8 T Cell-Mediated Neuroinflammation. Neurology(R) neuroimmunology & neuroinflammation 10: https://doi.org/10.1212/NXI.0000000000200117
Gross CC, Meyer C, Bhatia U, Yshii L, Kleffner I, Bauer J et al (2019) CD8(+) T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome. Nat Commun 10:5779. https://doi.org/10.1038/s41467-019-13593-5
doi: 10.1038/s41467-019-13593-5
pubmed: 31852955
pmcid: 6920411
Guo L, Bertola DR, Takanohashi A, Saito A, Segawa Y, Yokota T et al (2019) Bi-allelic CSF1R mutations cause skeletal dysplasia of dysosteosclerosis-pyle disease spectrum and degenerative encephalopathy with brain malformation. Am J Hum Genet 104:925–935. https://doi.org/10.1016/j.ajhg.2019.03.004
doi: 10.1016/j.ajhg.2019.03.004
pubmed: 30982609
pmcid: 6507048
Hahn JN, Kaushik DK, Mishra MK, Wang J, Silva C, Yong VW (2016) Impact of minocycline on extracellular matrix metalloproteinase inducer, a factor implicated in multiple sclerosis immunopathogenesis. J Immunol 197:3850–3860. https://doi.org/10.4049/jimmunol.1600436
doi: 10.4049/jimmunol.1600436
pubmed: 27733550
Halder SK, Milner R (2022) Exaggerated hypoxic vascular breakdown in aged brain due to reduced microglial vasculo-protection. Aging Cell 21:e13720. https://doi.org/10.1111/acel.13720
doi: 10.1111/acel.13720
pubmed: 36130175
pmcid: 9649604
Halder SK, Milner R (2020) Mild hypoxia triggers transient blood-brain barrier disruption: a fundamental protective role for microglia. Acta Neuropathol Commun 8:175. https://doi.org/10.1186/s40478-020-01051-z
doi: 10.1186/s40478-020-01051-z
pubmed: 33115539
pmcid: 7592567
Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A et al (2019) Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 50(253–271):e256. https://doi.org/10.1016/j.immuni.2018.11.004
doi: 10.1016/j.immuni.2018.11.004
Hannocks MJ, Zhang X, Gerwien H, Chashchina A, Burmeister M, Korpos E et al (2017) The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes. Matrix Biol 75–76:102–113. https://doi.org/10.1016/j.matbio.2017.11.007
doi: 10.1016/j.matbio.2017.11.007
pubmed: 29158162
Hao C-N, Geng Y-J, Li F, Yang T, Su D-F, Duan J-L et al (2011) Insulin-like growth factor-1 receptor activation prevents hydrogen peroxide-induced oxidative stress, mitochondrial dysfunction and apoptosis. Apoptosis 16:1118–1127. https://doi.org/10.1007/s10495-011-0634-9
doi: 10.1007/s10495-011-0634-9
pubmed: 21785846
Haruwaka K, Ikegami A, Tachibana Y, Ohno N, Konishi H, Hashimoto A et al (2019) Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat Commun 10:5816. https://doi.org/10.1038/s41467-019-13812-z
doi: 10.1038/s41467-019-13812-z
pubmed: 31862977
pmcid: 6925219
Hattori Y (2023) The microglia-blood vessel interactions in the developing brain. Neurosci Res 187:58–66. https://doi.org/10.1016/j.neures.2022.09.006
doi: 10.1016/j.neures.2022.09.006
pubmed: 36167249
Hawkes CA, McLaurin J (2009) Selective targeting of perivascular macrophages for clearance of β-amyloid in cerebral amyloid angiopathy. Proc Natl Acad Sci 106:1261–1266. https://doi.org/10.1073/pnas.0805453106
doi: 10.1073/pnas.0805453106
pubmed: 19164591
pmcid: 2633563
Howard R, Zubko O, Bradley R, Harper E, Pank L, O’Brien J et al (2020) Minocycline at 2 different dosages vs placebo for patients with mild alzheimer disease: a randomized clinical trial. JAMA Neurol 77:164–174. https://doi.org/10.1001/jamaneurol.2019.3762
doi: 10.1001/jamaneurol.2019.3762
pubmed: 31738372
Howland SW, Poh CM, Rénia L (2015) Activated brain endothelial cells cross-present malaria antigen. PLoS Pathog 11:e1004963. https://doi.org/10.1371/journal.ppat.1004963
doi: 10.1371/journal.ppat.1004963
pubmed: 26046849
pmcid: 4457820
Iadecola C, Smith EE, Anrather J, Gu C, Mishra A, Misra S, et al (2023) The Neurovasculome: Key Roles in Brain Health and Cognitive Impairment: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke 54: Doi https://doi.org/10.1161/str.0000000000000431
Jais A, Solas M, Backes H, Chaurasia B, Kleinridders A, Theurich S et al (2016) Myeloid-cell-derived VEGF maintains brain glucose uptake and limits cognitive impairment in obesity. Cell 166:1338–1340. https://doi.org/10.1016/j.cell.2016.08.010
doi: 10.1016/j.cell.2016.08.010
pubmed: 27565353
Jeong HW, Dieguez-Hurtado R, Arf H, Song J, Park H, Kruse K et al (2022) Single-cell transcriptomics reveals functionally specialized vascular endothelium in brain. Elife 11:e57520. https://doi.org/10.7554/eLife.57520
doi: 10.7554/eLife.57520
pubmed: 36197007
pmcid: 9566870
Jolivel V, Bicker F, Binamé F, Ploen R, Keller S, Gollan R et al (2015) Perivascular microglia promote blood vessel disintegration in the ischemic penumbra. Acta Neuropathol 129:279–295. https://doi.org/10.1007/s00401-014-1372-1
doi: 10.1007/s00401-014-1372-1
pubmed: 25500713
Jordao MJC, Sankowski R, Brendecke SM, Sagar, Locatelli G, Tai YH, Tay TL, et al (2019) Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation. Science 363: eaat7554 https://doi.org/10.1126/science.aat7554
Kenkhuis B, van Eekeren M, Parfitt DA, Ariyurek Y, Banerjee P, Priller J et al (2022) Iron accumulation induces oxidative stress, while depressing inflammatory polarization in human iPSC-derived microglia. Stem Cell Reports 17:1351–1365. https://doi.org/10.1016/j.stemcr.2022.04.006
doi: 10.1016/j.stemcr.2022.04.006
pubmed: 35523178
pmcid: 9213827
Kerkhofs D, van Hagen BT, Milanova IV, Schell KJ, van Essen H, Wijnands E et al (2020) Pharmacological depletion of microglia and perivascular macrophages prevents Vascular Cognitive Impairment in Ang II-induced hypertension. Theranostics 10:9512–9527. https://doi.org/10.7150/thno.44394
doi: 10.7150/thno.44394
pubmed: 32863942
pmcid: 7449902
Kida S, Steart PV, Zhang E-T, Weller RO (1993) Perivascular cells act as scavengers in the cerebral perivascular spaces and remain distinct from pericytes, microglia and macrophages. Acta Neuropathol 85:646–652. https://doi.org/10.1007/BF00334675
doi: 10.1007/BF00334675
pubmed: 8337943
Kohler E, Prentice DA, Bates TR, Hankey GJ, Claxton A, van Heerden J et al (2013) Intravenous minocycline in acute stroke: a randomized, controlled pilot study and meta-analysis. Stroke 44:2493–2499. https://doi.org/10.1161/strokeaha.113.000780
doi: 10.1161/strokeaha.113.000780
pubmed: 23868273
Lei F, Cui N, Zhou C, Chodosh J, Vavvas DG, Paschalis EI (2020) CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages. Proc Natl Acad Sci U S A 117:23336–23338. https://doi.org/10.1073/pnas.1922788117
doi: 10.1073/pnas.1922788117
pubmed: 32900927
pmcid: 7519218
Li Y, He X, Kawaguchi R, Zhang Y, Wang Q, Monavarfeshani A et al (2020) Microglia-organized scar-free spinal cord repair in neonatal mice. Nature 587:613–618. https://doi.org/10.1038/s41586-020-2795-6
doi: 10.1038/s41586-020-2795-6
pubmed: 33029008
pmcid: 7704837
Li Y, Zou C, Chen C, Li S, Zhu Z, Fan Q et al (2023) Myeloid-derived MIF drives RIPK1-mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury. Proc Natl Acad Sci USA 120:e2219091120. https://doi.org/10.1073/pnas.2219091120
doi: 10.1073/pnas.2219091120
pubmed: 36693098
pmcid: 9945963
Lin X, Khalin I, Harapan BN, Terpolilli NA, Schwarting J, Plesnila N (2023) Perivascular macrophages mediate microvasospasms after experimental subarachnoid hemorrhage. Stroke 54:2126–2134. https://doi.org/10.1161/STROKEAHA.122.042290
doi: 10.1161/STROKEAHA.122.042290
pubmed: 37325921
Liu Z, Shi H, Xu J, Yang Q, Ma Q, Mao X, et al (2022) Single-cell transcriptome analyses reveal microglia types associated with proliferative retinopathy. JCI Insight 7: https://doi.org/10.1172/jci.insight.160940
Lopes Pinheiro MA, Kamermans A, Garcia-Vallejo JJ, van Het Hof B, Wierts L, O'Toole T, et al (2016) Internalization and presentation of myelin antigens by the brain endothelium guides antigen-specific T cell migration. Elife 5: https://doi.org/10.7554/eLife.13149
Lückoff A, Caramoy A, Scholz R, Prinz M, Kalinke U, Langmann T (2016) Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization. EMBO Mol Med 8:670–678. https://doi.org/10.15252/emmm.201505994
doi: 10.15252/emmm.201505994
pubmed: 27137488
pmcid: 4888856
Luo Q, Jiang Z, Jiang J, Wan L, Li Y, Huang Y et al (2023) Tsp-1(+) microglia attenuate retinal neovascularization by maintaining the expression of Smad3 in endothelial cells through exosomes with decreased miR-27a-5p. Theranostics 13:3689–3706. https://doi.org/10.7150/thno.84236
doi: 10.7150/thno.84236
pubmed: 37441592
pmcid: 10334831
Mastorakos P, Mihelson N, Luby M, Burks SR, Johnson K, Hsia AW et al (2021) Temporally distinct myeloid cell responses mediate damage and repair after cerebrovascular injury. Nat Neurosci 24:245–258. https://doi.org/10.1038/s41593-020-00773-6
doi: 10.1038/s41593-020-00773-6
pubmed: 33462481
pmcid: 7854523
Masuda T, Amann L, Monaco G, Sankowski R, Staszewski O, Krueger M et al (2022) Specification of CNS macrophage subsets occurs postnatally in defined niches. Nature 604:740–748. https://doi.org/10.1038/s41586-022-04596-2
doi: 10.1038/s41586-022-04596-2
pubmed: 35444273
Masuda T, Amann L, Sankowski R, Staszewski O, Lenz M, P DE, Snaidero N, et al (2020) Novel Hexb-based tools for studying microglia in the CNS. Nat Immunol 21: 802-815 Doi https://doi.org/10.1038/s41590-020-0707-4
Masuda T, Croom D, Hida H, Kirov SA (2011) Capillary blood flow around microglial somata determines dynamics of microglial processes in ischemic conditions. Glia 59:1744–1753. https://doi.org/10.1002/glia.21220
doi: 10.1002/glia.21220
pubmed: 21800362
pmcid: 3174346
Mato M, Ookawara S, Kurihara K (1980) Uptake of exogenous substances and marked infoldings of the fluorescent granular pericyte in cerebral fine vessels. Am J Anatomy 157:329–332. https://doi.org/10.1002/aja.1001570308
doi: 10.1002/aja.1001570308
Mato M, Ookawara S, Sakamoto A, Aikawa E, Ogawa T, Mitsuhashi U et al (1996) Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex. Proc Natl Acad Sci U S A 93:3269–3274. https://doi.org/10.1073/pnas.93.8.3269
doi: 10.1073/pnas.93.8.3269
pubmed: 8622926
pmcid: 39595
McCarron RM, Racke M, Spatz M, McFarlin DE (1991) Cerebral vascular endothelial cells are effective targets for in vitro lysis by encephalitogenic T lymphocytes. J Immunol 147:503–508
doi: 10.4049/jimmunol.147.2.503
pubmed: 1712809
Mendes-Jorge L, Ramos D, Luppo M, Llombart C, Alexandre-Pires G, Nacher V et al (2009) Scavenger function of resident autofluorescent perivascular macrophages and their contribution to the maintenance of the blood-retinal barrier. Invest Ophthalmol Vis Sci 50:5997–6005. https://doi.org/10.1167/iovs.09-3515
doi: 10.1167/iovs.09-3515
pubmed: 19608545
Mills SA, Jobling AI, Dixon MA, Bui BV, Vessey KA, Phipps JA, et al (2021) Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy. Proc Natl Acad Sci U S A 118: https://doi.org/10.1073/pnas.2112561118
Mundt S, Greter M, Flugel A, Becher B (2019) The CNS immune landscape from the viewpoint of a T cell. Trends Neurosci 42:667–679. https://doi.org/10.1016/j.tins.2019.07.008
doi: 10.1016/j.tins.2019.07.008
pubmed: 31474310
Murinello S, Usui Y, Sakimoto S, Kitano M, Aguilar E, Friedlander HM et al (2019) miR-30a-5p inhibition promotes interaction of Fas(+) endothelial cells and FasL(+) microglia to decrease pathological neovascularization and promote physiological angiogenesis. Glia 67:332–344. https://doi.org/10.1002/glia.23543
doi: 10.1002/glia.23543
pubmed: 30484883
Nemeth DP, Liu X, McKim DB, DiSabato DJ, Oliver B, Herd A et al (2022) Dynamic interleukin-1 receptor type 1 signaling mediates microglia-vasculature interactions following repeated systemic LPS. J Inflamm Res 15:1575–1590. https://doi.org/10.2147/jir.S350114
doi: 10.2147/jir.S350114
pubmed: 35282272
pmcid: 8906862
Niu J, Tsai H-H, Hoi KK, Huang N, Yu G, Kim K et al (2019) Aberrant oligodendroglial–vascular interactions disrupt the blood–brain barrier, triggering CNS inflammation. Nat Neurosci 22:709–718. https://doi.org/10.1038/s41593-019-0369-4
doi: 10.1038/s41593-019-0369-4
pubmed: 30988524
pmcid: 6486410
Nuki Y, Matsumoto MM, Tsang E, Young WL, Van Rooijen N, Kurihara C et al (2009) Roles of macrophages in flow-induced outward vascular remodeling. J Cereb Blood Flow Metab 29:495–503. https://doi.org/10.1038/jcbfm.2008.136
doi: 10.1038/jcbfm.2008.136
pubmed: 19002198
Panahi M, Hase Y, Gallart-Palau X, Mitra S, Watanabe A, Low RC et al (2023) ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics. Acta Neuropathol Commun 11:76. https://doi.org/10.1186/s40478-023-01558-1
doi: 10.1186/s40478-023-01558-1
pubmed: 37158955
pmcid: 10169505
Paolicelli RC, Sierra A, Stevens B, Tremblay M-E, Aguzzi A, Ajami B et al (2022) Microglia states and nomenclature: a field at its crossroads. Neuron 110:3458–3483. https://doi.org/10.1016/j.neuron.2022.10.020
doi: 10.1016/j.neuron.2022.10.020
pubmed: 36327895
pmcid: 9999291
Pardigon N, Bercovici N, Calbo S, Santos-Lima EC, Liblau R, Kourilsky P et al (1998) Role of co-stimulation in CD8+ T cell activation. Int Immunol 10:619–630. https://doi.org/10.1093/intimm/10.5.619
doi: 10.1093/intimm/10.5.619
pubmed: 9645610
Park L, Uekawa K, Garcia-Bonilla L, Koizumi K, Murphy M, Pistik R et al (2017) Brain perivascular macrophages initiate the neurovascular dysfunction of alzheimer abeta peptides. Circ Res 121:258–269. https://doi.org/10.1161/circresaha.117.311054
doi: 10.1161/circresaha.117.311054
pubmed: 28515043
pmcid: 5522360
Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR 3rd, Lafaille JJ et al (2013) Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155:1596–1609. https://doi.org/10.1016/j.cell.2013.11.030
doi: 10.1016/j.cell.2013.11.030
pubmed: 24360280
pmcid: 4033691
Pedragosa J, Salas-Perdomo A, Gallizioli M, Cugota R, Miro-Mur F, Brianso F et al (2018) CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage. Acta Neuropathol Commun 6:76. https://doi.org/10.1186/s40478-018-0581-6
doi: 10.1186/s40478-018-0581-6
pubmed: 30092836
pmcid: 6083589
Peng W, Achariyar TM, Li B, Liao Y, Mestre H, Hitomi E et al (2016) Suppression of glymphatic fluid transport in a mouse model of Alzheimer’s disease. Neurobiol Dis 93:215–225. https://doi.org/10.1016/j.nbd.2016.05.015
doi: 10.1016/j.nbd.2016.05.015
pubmed: 27234656
pmcid: 4980916
Peng W, Wan L, Luo Z, Xie Y, Liu Y, Huang T et al (2021) Microglia-derived exosomes improve spinal cord functional recovery after injury via inhibiting oxidative stress and promoting the survival and function of endothelia cells. Oxid Med Cell Longev 2021:1695087. https://doi.org/10.1155/2021/1695087
doi: 10.1155/2021/1695087
pubmed: 34484559
pmcid: 8413072
Pesic M, Bartholomaus I, Kyratsous NI, Heissmeyer V, Wekerle H et al (2013) 2-photon imaging of phagocyte-mediated T cell activation in the CNS. J Clin Invest 123:1192–1201. https://doi.org/10.1172/JCI67233
doi: 10.1172/JCI67233
pubmed: 23454769
pmcid: 3582148
Plein A, Fantin A, Denti L, Pollard JW, Ruhrberg C (2018) Erythro-myeloid progenitors contribute endothelial cells to blood vessels. Nature 562:223–228. https://doi.org/10.1038/s41586-018-0552-x
doi: 10.1038/s41586-018-0552-x
pubmed: 30258231
pmcid: 6289247
Rajan WD, Wojtas B, Gielniewski B, Miro-Mur F, Pedragosa J, Zawadzka M et al (2020) Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans. Neurobiol Dis 137:104722. https://doi.org/10.1016/j.nbd.2019.104722
doi: 10.1016/j.nbd.2019.104722
pubmed: 31926295
Razakandrainibe R, Pelleau S, Grau GE, Jambou R (2012) Antigen presentation by endothelial cells: What role in the pathophysiology of malaria? Trends Parasitol 28:151–160. https://doi.org/10.1016/j.pt.2012.01.004
doi: 10.1016/j.pt.2012.01.004
pubmed: 22365903
Riba M, Auge E, Campo-Sabariz J, Moral-Anter D, Molina-Porcel L, Ximelis T et al (2019) Corpora amylacea act as containers that remove waste products from the brain. Proc Natl Acad Sci U S A 116:26038–26048. https://doi.org/10.1073/pnas.1913741116
doi: 10.1073/pnas.1913741116
pubmed: 31796594
pmcid: 6926005
Riba M, Campo-Sabariz J, Tena I, Molina-Porcel L, Ximelis T, Calvo M et al (2022) Wasteosomes (corpora amylacea) of human brain can be phagocytosed and digested by macrophages. Cell Biosci 12:177. https://doi.org/10.1186/s13578-022-00915-2
doi: 10.1186/s13578-022-00915-2
pubmed: 36307854
pmcid: 9617366
Riggle BA, Manglani M, Maric D, Johnson KR, Lee MH, Neto OLA et al (2020) CD8+ T cells target cerebrovasculature in children with cerebral malaria. J Clin Invest 130:1128–1138. https://doi.org/10.1172/JCI133474
doi: 10.1172/JCI133474
pubmed: 31821175
pmcid: 7269583
Risau W, Engelhardt B, Wekerle H (1990) Immune function of the blood-brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro. J Cell Biol 110:1757–1766. https://doi.org/10.1083/jcb.110.5.1757
doi: 10.1083/jcb.110.5.1757
pubmed: 1692329
Roman Sankowski PS, Alexander Benkendorff,, Chotima Böttcher CF-Z, Chintan Chhatbar,, Jonathan Cahueau GM, Adrià Dalmau Gasull,, et al (2023) Multiomic spatial landscape of innate immune cells at human central nervous system borders. Nat Med in print: https://doi.org/10.1038/s41591-023-02673-1
Roubeix C, Dominguez E, Raoul W, Guillonneau X, Paques M, Sahel J-A et al (2019) Mo-derived perivascular macrophage recruitment protects against endothelial cell death in retinal vein occlusion. J Neuroinflammation 16:157. https://doi.org/10.1186/s12974-019-1547-8
doi: 10.1186/s12974-019-1547-8
pubmed: 31351497
pmcid: 6660930
Ryan SK, Zelic M, Han Y, Teeple E, Chen L, Sadeghi M et al (2023) Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration. Nat Neurosci 26:12–26. https://doi.org/10.1038/s41593-022-01221-3
doi: 10.1038/s41593-022-01221-3
pubmed: 36536241
Ryu JK, Rafalski VA, Meyer-Franke A, Adams RA, Poda SB, Rios Coronado PE et al (2018) Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration. Nat Immunol 19:1212–1223. https://doi.org/10.1038/s41590-018-0232-x
doi: 10.1038/s41590-018-0232-x
pubmed: 30323343
pmcid: 6317891
Santisteban MM, Ahn SJ, Lane D, Faraco G, Garcia-Bonilla L, Racchumi G et al (2020) Endothelium-macrophage crosstalk mediates blood-brain barrier dysfunction in hypertension. Hypertension 76:795–807. https://doi.org/10.1161/hypertensionaha.120.15581
doi: 10.1161/hypertensionaha.120.15581
pubmed: 32654560
Santisteban MM, Schaeffer S, Anfray A, Faraco G, Brea D, Wang G et al (2024) Meningeal interleukin-17-producing T cells mediate cognitive impairment in a mouse model of salt-sensitive hypertension. Nat Neurosci 27:63–77. https://doi.org/10.1038/s41593-023-01497-z
doi: 10.1038/s41593-023-01497-z
pubmed: 38049579
Schaeffer S, Iadecola C (2021) Revisiting the neurovascular unit. Nat Neurosci 24:1198–1209. https://doi.org/10.1038/s41593-021-00904-7
doi: 10.1038/s41593-021-00904-7
pubmed: 34354283
pmcid: 9462551
Schoch HJ, Fischer S, Marti HH (2002) Hypoxia-induced vascular endothelial growth factor expression causes vascular leakage in the brain. Brain 125:2549–2557. https://doi.org/10.1093/brain/awf257
doi: 10.1093/brain/awf257
pubmed: 12390979
Sedgwick JD, Hughes CC, Male DK, MacPhee IA, ter Meulen V (1990) Antigen-specific damage to brain vascular endothelial cells mediated by encephalitogenic and nonencephalitogenic CD4+ T cell lines in vitro. J Immunol 145:2474–2481
doi: 10.4049/jimmunol.145.8.2474
pubmed: 1698855
Shi D, Sheng A, Chi L (2021) Glycosaminoglycan-protein interactions and their roles in human disease. Front Mol Biosci 8:639666. https://doi.org/10.3389/fmolb.2021.639666
doi: 10.3389/fmolb.2021.639666
pubmed: 33768117
pmcid: 7985165
Sobel RA, Blanchette BW, Bhan AK, Colvin RB (1984) The immunopathology of experimental allergic encephalomyelitis. II. Endothelial cell Ia increases prior to inflammatory cell infiltration. J Immunol 132:2402–2407
doi: 10.4049/jimmunol.132.5.2402
pubmed: 6425402
Spiteri AG, Ni D, Ling ZL, Macia L, Campbell IL, Hofer MJ et al (2022) PLX5622 reduces disease severity in lethal cns infection by off-target inhibition of peripheral inflammatory monocyte production. Front Immunol 13:851556. https://doi.org/10.3389/fimmu.2022.851556
doi: 10.3389/fimmu.2022.851556
pubmed: 35401512
pmcid: 8990748
Sumi N, Nishioku T, Takata F, Matsumoto J, Watanabe T, Shuto H et al (2010) Lipopolysaccharide-activated microglia induce dysfunction of the blood-brain barrier in rat microvascular endothelial cells co-cultured with microglia. Cell Mol Neurobiol 30:247–253. https://doi.org/10.1007/s10571-009-9446-7
doi: 10.1007/s10571-009-9446-7
pubmed: 19728078
Szalay G, Martinecz B, Lenart N, Kornyei Z, Orsolits B, Judak L et al (2016) Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke. Nat Commun 7:11499. https://doi.org/10.1038/ncomms11499
doi: 10.1038/ncomms11499
pubmed: 27139776
pmcid: 4857403
Taylor RA, Chang C-F, Goods BA, Hammond MD, Grory BM, Ai Y et al (2016) TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage. J Clin Investig 127:280–292. https://doi.org/10.1172/jci88647
doi: 10.1172/jci88647
pubmed: 27893460
pmcid: 5199690
Taylor X, Clark IM, Fitzgerald GJ, Oluoch H, Hole JT, Demattos RB et al (2023) Amyloid-β (Aβ) immunotherapy induced microhemorrhages are associated with activated perivascular macrophages and peripheral monocyte recruitment in Alzheimer’s disease mice. Mol Neurodegener 18:59. https://doi.org/10.1186/s13024-023-00649-w
doi: 10.1186/s13024-023-00649-w
pubmed: 37649100
pmcid: 10469415
Thurgur H, Pinteaux E (2019) Microglia in the neurovascular unit: blood-brain barrier–microglia interactions after central nervous system disorders. Neuroscience 405:55–67. https://doi.org/10.1016/j.neuroscience.2018.06.046
doi: 10.1016/j.neuroscience.2018.06.046
pubmed: 31007172
Uekawa K, Hattori Y, Ahn SJ, Seo J, Casey N, Anfray A, et al (2023) Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress. Molecular Neurodegeneration 18: https://doi.org/10.1186/s13024-023-00660-1
Vanlandewijck M, He L, Mae MA, Andrae J, Ando K, Gaudio F et al (2018) A molecular atlas of cell types and zonation in the brain vasculature. Nature 554:475–480. https://doi.org/10.1038/nature25739
doi: 10.1038/nature25739
pubmed: 29443965
Vass K, Lassmann H, Wekerle H, Wisniewski HM (1986) The distribution of Ia antigen in the lesions of rat acute experimental allergic encephalomyelitis. Acta Neuropathol 70:149–160. https://doi.org/10.1007/BF00691433
doi: 10.1007/BF00691433
pubmed: 3488634
Wan H, Brathwaite S, Ai J, Hynynen K, Macdonald RL (2021) Role of perivascular and meningeal macrophages in outcome following experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab 41:1842–1857. https://doi.org/10.1177/0271678x20980296
doi: 10.1177/0271678x20980296
pubmed: 33444089
pmcid: 8327101
Welser JV, Li L, Milner R (2010) Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of TNF and TGF-β1. J Neuroinflammation 7:89. https://doi.org/10.1186/1742-2094-7-89
doi: 10.1186/1742-2094-7-89
pubmed: 21134289
pmcid: 3016272
Wenzel J, Hansen CE, Bettoni C, Vogt MA, Lembrich B, Natsagdorj R et al (2020) Impaired endothelium-mediated cerebrovascular reactivity promotes anxiety and respiration disorders in mice. Proc Natl Acad Sci U S A 117:1753–1761. https://doi.org/10.1073/pnas.1907467117
doi: 10.1073/pnas.1907467117
pubmed: 31896584
pmcid: 6983400
Willis CL, Garwood CJ, Ray DE (2007) A size selective vascular barrier in the rat area postrema formed by perivascular macrophages and the extracellular matrix. Neuroscience 150:498–509. https://doi.org/10.1016/j.neuroscience.2007.09.023
doi: 10.1016/j.neuroscience.2007.09.023
pubmed: 17945430
Wong R, Lenart N, Hill L, Toms L, Coutts G, Martinecz B et al (2019) Interleukin-1 mediates ischaemic brain injury via distinct actions on endothelial cells and cholinergic neurons. Brain Behav Immun 76:126–138. https://doi.org/10.1016/j.bbi.2018.11.012
doi: 10.1016/j.bbi.2018.11.012
pubmed: 30453020
pmcid: 6363965
Wu C, Shi L, Ma Y, Pan Y, Wang L, Chen S et al (2023) Construction and optimization of a coculture system of mouse brain microvascular endothelial cells and myelin debris. Neurosci Lett 811:137345. https://doi.org/10.1016/j.neulet.2023.137345
doi: 10.1016/j.neulet.2023.137345
pubmed: 37308055
Wu YC, Bogale TA, Koistinaho J, Pizzi M, Rolova T, Bellucci A (2024) β-amyloid, Tau and α-synuclein versus brain macrophages, endothelial cells and pericytes: the engineers of blood-brain barrier dysfunction in acute and chronic neurological disorders. Acta Neuropathol:
Xie L, Zhao H, Wang Y, Chen Z (2020) Exosomal shuttled miR-424-5p from ischemic preconditioned microglia mediates cerebral endothelial cell injury through negatively regulation of FGF2/STAT3 pathway. Exp Neurol 333:113411. https://doi.org/10.1016/j.expneurol.2020.113411
doi: 10.1016/j.expneurol.2020.113411
pubmed: 32707150
Xingi E, Koutsoudaki PN, Thanou I, Phan MS, Margariti M, Scheller A, et al. (2023) LPS-Induced Systemic Inflammation Affects the Dynamic Interactions of Astrocytes and Microglia with the Vasculature of the Mouse Brain Cortex. Cells 12: Doi ARTN 1418 https://doi.org/10.3390/cells12101418
Yamamoto Y, Craggs LJ, Watanabe A, Booth T, Attems J, Low RW et al (2013) Brain microvascular accumulation and distribution of the NOTCH3 ectodomain and granular osmiophilic material in CADASIL. J Neuropathol Exp Neurol 72:416–431. https://doi.org/10.1097/NEN.0b013e31829020b5
doi: 10.1097/NEN.0b013e31829020b5
pubmed: 23584202
Yao C, Cao Y, Wang D, Lv Y, Liu Y, Gu X et al (2022) Single-cell sequencing reveals microglia induced angiogenesis by specific subsets of endothelial cells following spinal cord injury. FASEB J 36:e22393. https://doi.org/10.1096/fj.202200337R
doi: 10.1096/fj.202200337R
pubmed: 35699080
Yenari MA, Xu L, Tang XN, Qiao Y, Giffard RG (2006) Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke 37:1087–1093. https://doi.org/10.1161/01.STR.0000206281.77178.ac
doi: 10.1161/01.STR.0000206281.77178.ac
pubmed: 16497985
Yu Z, Fang X, Liu W, Sun R, Zhou J, Pu Y et al (2022) Microglia regulate blood-brain barrier integrity via MiR-126a-5p/MMP9 axis during inflammatory demyelination. Advanced Science 9:2105442. https://doi.org/10.1002/advs.202105442
doi: 10.1002/advs.202105442
pubmed: 35758549
pmcid: 9403646
Zarb Y, Sridhar S, Nassiri S, Utz SG, Schaffenrath J, Maheshwari U, et al (2021) Microglia control small vessel calcification via TREM2. Sci Adv 7: https://doi.org/10.1126/sciadv.abc4898
Zhang L, Wei W, Ai X, Kilic E, Hermann DM, Venkataramani V et al (2021) Extracellular vesicles from hypoxia-preconditioned microglia promote angiogenesis and repress apoptosis in stroke mice via the TGF-β/Smad2/3 pathway. Cell Death Dis 12:1068. https://doi.org/10.1038/s41419-021-04363-7
doi: 10.1038/s41419-021-04363-7
pubmed: 34753919
pmcid: 8578653
Zhang N, Kim SH, Gainullina A, Erlich EC, Onufer EJ, Kim J, et al (2021) LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth. J Exp Med 218: https://doi.org/10.1084/jem.20210924
Zhao X, Eyo UB, Murugan M, Wu LJ (2018) Microglial interactions with the neurovascular system in physiology and pathology. Dev Neurobiol 78:604–617. https://doi.org/10.1002/dneu.22576
doi: 10.1002/dneu.22576
pubmed: 29318762
pmcid: 5980686
Zhou T, Zheng Y, Sun L, Badea SR, Jin Y, Liu Y et al (2019) Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury. Nat Neurosci 22:421–435. https://doi.org/10.1038/s41593-018-0324-9
doi: 10.1038/s41593-018-0324-9
pubmed: 30664769
pmcid: 6913093
Zille M, Ikhsan M, Jiang Y, Lampe J, Wenzel J, Schwaninger M (2019) The impact of endothelial cell death in the brain and its role after stroke: a systematic review. Cell Stress 3:330–347. https://doi.org/10.15698/cst2019.11.203
doi: 10.15698/cst2019.11.203
pubmed: 31799500
pmcid: 6859425