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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Emerging Roles of Microglia in Blood-Brain Barrier Integrity in Aging and Neurodegeneration

Author(s): Simeng Zhang, Rui Meng, Muzhou Jiang*, Hong Qing* and Junjun Ni*

Volume 22, Issue 7, 2024

Published on: 01 September, 2023

Page: [1189 - 1204] Pages: 16

DOI: 10.2174/1570159X21666230203103910

Price: $65

Open Access Journals Promotions 2
Abstract

The blood-brain barrier (BBB) is a highly selective interface between the blood and the brain parenchyma. It plays an essential role in maintaining a specialized environment for central nervous system function and homeostasis. The BBB disrupts with age, which contributes to the development of many age-related disorders due to central and peripheral toxic factors or BBB dysfunction. Microglia, the resident innate immune cells of the brain, have recently been explored for their ability to directly and indirectly regulate the integrity of the BBB. This review will focus on the current understanding of the molecular mechanisms utilized by microglia to regulate BBB integrity and how this becomes disrupted in aging and age-associated diseases. We will also discuss the rationale for considering microglia as a therapeutic target to prevent or slow down neurodegeneration.

Keywords: Microglia, neuroinflammation, blood-brain barrier, neurovascular unit, aging, neurodegeneration.

Graphical Abstract
[1]
Banks, W.A.; Reed, M.J.; Logsdon, A.F.; Rhea, E.M.; Erickson, M.A. Healthy aging and the blood–brain barrier. Nature Aging, 2021, 1(3), 243-254.
[http://dx.doi.org/10.1038/s43587-021-00043-5] [PMID: 34368785]
[2]
Senatorov, V.V., Jr; Friedman, A.R.; Milikovsky, D.Z.; Ofer, J.; Saar-Ashkenazy, R.; Charbash, A.; Jahan, N.; Chin, G.; Mihaly, E.; Lin, J.M.; Ramsay, H.J.; Moghbel, A.; Preininger, M.K.; Eddings, C.R.; Harrison, H.V.; Patel, R.; Shen, Y.; Ghanim, H.; Sheng, H.; Veksler, R.; Sudmant, P.H.; Becker, A.; Hart, B.; Rogawski, M.A.; Dillin, A.; Friedman, A.; Kaufer, D. Blood-brain barrier dysfunction in aging induces hyperactivation of TGFβ signaling and chronic yet reversible neural dysfunction. Sci. Transl. Med., 2019, 11(521), eaaw8283.
[http://dx.doi.org/10.1126/scitranslmed.aaw8283] [PMID: 31801886]
[3]
Bell, R.D.; Zlokovic, B.V. Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease. Acta Neuropathol., 2009, 118(1), 103-113.
[http://dx.doi.org/10.1007/s00401-009-0522-3] [PMID: 19319544]
[4]
Sagare, A.P.; Bell, R.D.; Zlokovic, B.V. Neurovascular dysfunction and faulty amyloid β-peptide clearance in Alzheimer disease. Cold Spring Harb. Perspect. Med., 2012, 2(10), a011452.
[http://dx.doi.org/10.1101/cshperspect.a011452] [PMID: 23028132]
[5]
Sweeney, M.D.; Sagare, A.P.; Zlokovic, B.V. Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol., 2018, 14(3), 133-150.
[http://dx.doi.org/10.1038/nrneurol.2017.188] [PMID: 29377008]
[6]
Nation, D.A.; Sweeney, M.D.; Montagne, A.; Sagare, A.P.; D’Orazio, L.M.; Pachicano, M.; Sepehrband, F.; Nelson, A.R.; Buennagel, D.P.; Harrington, M.G.; Benzinger, T.L.S.; Fagan, A.M.; Ringman, J.M.; Schneider, L.S.; Morris, J.C.; Chui, H.C.; Law, M.; Toga, A.W.; Zlokovic, B.V. Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat. Med., 2019, 25(2), 270-276.
[http://dx.doi.org/10.1038/s41591-018-0297-y] [PMID: 30643288]
[7]
Prinz, M.; Priller, J. Microglia and brain macrophages in the molecular age: From origin to neuropsychiatric disease. Nat. Rev. Neurosci., 2014, 15(5), 300-312.
[http://dx.doi.org/10.1038/nrn3722] [PMID: 24713688]
[8]
Butler, C.A.; Popescu, A.S.; Kitchener, E.J.A.; Allendorf, D.H.; Puigdellívol, M.; Brown, G.C. Microglial phagocytosis of neurons in neurodegeneration, and its regulation. J. Neurochem., 2021, 158(3), 621-639.
[http://dx.doi.org/10.1111/jnc.15327] [PMID: 33608912]
[9]
Krasemann, S.; Madore, C.; Cialic, R.; Baufeld, C.; Calcagno, N.; El Fatimy, R.; Beckers, L.; O’Loughlin, E.; Xu, Y.; Fanek, Z.; Greco, D.J.; Smith, S.T.; Tweet, G.; Humulock, Z.; Zrzavy, T.; Conde-Sanroman, P.; Gacias, M.; Weng, Z.; Chen, H.; Tjon, E.; Mazaheri, F.; Hartmann, K.; Madi, A.; Ulrich, J.D.; Glatzel, M.; Worthmann, A.; Heeren, J.; Budnik, B.; Lemere, C.; Ikezu, T.; Heppner, F.L.; Litvak, V.; Holtzman, D.M.; Lassmann, H.; Weiner, H.L.; Ochando, J.; Haass, C.; Butovsky, O. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity, 2017, 47(3), 566-581.e9.
[http://dx.doi.org/10.1016/j.immuni.2017.08.008] [PMID: 28930663]
[10]
Jha, M.K.; Jo, M.; Kim, J.H.; Suk, K. Microglia-astrocyte crosstalk: An intimate molecular conversation. Neuroscientist, 2019, 25(3), 227-240.
[http://dx.doi.org/10.1177/1073858418783959] [PMID: 29931997]
[11]
Peferoen, L.; Kipp, M.; van der Valk, P.; van Noort, J.M.; Amor, S. Oligodendrocyte-microglia cross-talk in the central nervous system. Immunology, 2014, 141(3), 302-313.
[http://dx.doi.org/10.1111/imm.12163] [PMID: 23981039]
[12]
Xie, Z.; Meng, J.; Wu, Z.; Nakanishi, H.; Hayashi, Y.; Kong, W.; Lan, F. Narengaowa; Yang, Q.; Qing, H.; Ni, J. The dual nature of microglia in Alzheimer’s disease: A microglia-neuron crosstalk perspective. Neuroscientist, 2022, 10738584211070273.
[http://dx.doi.org/10.1177/10738584211070273] [PMID: 35348415]
[13]
Ehrlich, P. The body’s need for oxygen.In: A color analytical study; Hirschwald, Berlin; , 1885.
[14]
Liebner, S.; Dijkhuizen, R.M.; Reiss, Y.; Plate, K.H.; Agalliu, D.; Constantin, G. Functional morphology of the blood–brain barrier in health and disease. Acta Neuropathol., 2018, 135(3), 311-336.
[http://dx.doi.org/10.1007/s00401-018-1815-1] [PMID: 29411111]
[15]
Wosik, K.; Cayrol, R.; Dodelet-Devillers, A.; Berthelet, F.; Bernard, M.; Moumdjian, R.; Bouthillier, A.; Reudelhuber, T.L.; Prat, A. Angiotensin II controls occludin function and is required for blood brain barrier maintenance: relevance to multiple sclerosis. J. Neurosci., 2007, 27(34), 9032-9042.
[http://dx.doi.org/10.1523/JNEUROSCI.2088-07.2007] [PMID: 17715340]
[16]
Dong, X. Current strategies for brain drug delivery. Theranostics, 2018, 8(6), 1481-1493.
[http://dx.doi.org/10.7150/thno.21254] [PMID: 29556336]
[17]
Gonzales, M.M.; Garbarino, V.R.; Pollet, E.; Palavicini, J.P.; Kellogg, D.L., Jr; Kraig, E.; Orr, M.E. Biological aging processes underlying cognitive decline and neurodegenerative disease. J. Clin. Invest., 2022, 132(10), e158453.
[http://dx.doi.org/10.1172/JCI158453] [PMID: 35575089]
[18]
Verheggen, I.C.M.; de Jong, J.J.A.; van Boxtel, M.P.J.; Postma, A.A.; Jansen, J.F.A.; Verhey, F.R.J.; Backes, W.H. Imaging the role of blood–brain barrier disruption in normal cognitive ageing. Geroscience, 2020, 42(6), 1751-1764.
[http://dx.doi.org/10.1007/s11357-020-00282-1] [PMID: 33025410]
[19]
Rubin, L.L.; Staddon, J.M. The cell biology of the blood-brain barrier. Annu. Rev. Neurosci., 1999, 22(1), 11-28.
[http://dx.doi.org/10.1146/annurev.neuro.22.1.11] [PMID: 10202530]
[20]
Runkle, E.A.; Mu, D. Tight junction proteins: From barrier to tumorigenesis. Cancer Lett., 2013, 337(1), 41-48.
[http://dx.doi.org/10.1016/j.canlet.2013.05.038] [PMID: 23743355]
[21]
Thurgur, H.; Pinteaux, E. Microglia in the neurovascular unit: Blood–brain barrier–microglia interactions after central nervous system disorders. Neuroscience, 2019, 405, 55-67.
[http://dx.doi.org/10.1016/j.neuroscience.2018.06.046] [PMID: 31007172]
[22]
Balda, M.S.; Whitney, J.A.; Flores, C.; González, S.; Cereijido, M.; Matter, K. Functional dissociation of paracellular permeability and transepithelial electrical resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J. Cell Biol., 1996, 134(4), 1031-1049.
[http://dx.doi.org/10.1083/jcb.134.4.1031] [PMID: 8769425]
[23]
Yamamoto, M.; Ramirez, S.H.; Sato, S.; Kiyota, T.; Cerny, R.L.; Kaibuchi, K.; Persidsky, Y.; Ikezu, T. Phosphorylation of claudin-5 and occludin by rho kinase in brain endothelial cells. Am. J. Pathol., 2008, 172(2), 521-533.
[http://dx.doi.org/10.2353/ajpath.2008.070076] [PMID: 18187566]
[24]
Engelhardt, B.; Liebner, S. Novel insights into the development and maintenance of the blood–brain barrier. Cell Tissue Res., 2014, 355(3), 687-699.
[http://dx.doi.org/10.1007/s00441-014-1811-2] [PMID: 24590145]
[25]
Rossa, J.; Ploeger, C.; Vorreiter, F.; Saleh, T.; Protze, J.; Günzel, D.; Wolburg, H.; Krause, G.; Piontek, J. Claudin-3 and claudin-5 protein folding and assembly into the tight junction are controlled by non-conserved residues in the transmembrane 3 (TM3) and extracellular loop 2 (ECL2) segments. J. Biol. Chem., 2014, 289(11), 7641-7653.
[http://dx.doi.org/10.1074/jbc.M113.531012] [PMID: 24478310]
[26]
Harris, T.J.C.; Tepass, U. Adherens junctions: From molecules to morphogenesis. Nat. Rev. Mol. Cell Biol., 2010, 11(7), 502-514.
[http://dx.doi.org/10.1038/nrm2927] [PMID: 20571587]
[27]
Zhao, F.; Zhong, L.; Luo, Y. Endothelial glycocalyx as an important factor in composition of blood-brain barrier. CNS Neurosci. Ther., 2021, 27(1), 26-35.
[http://dx.doi.org/10.1111/cns.13560] [PMID: 33377610]
[28]
Henry, C.B.S.; Duling, B.R. TNF-α increases entry of macromolecules into luminal endothelial cell glycocalyx. Am. J. Physiol. Heart Circ. Physiol., 2000, 279(6), H2815-H2823.
[http://dx.doi.org/10.1152/ajpheart.2000.279.6.H2815] [PMID: 11087236]
[29]
Sofroniew, M.V.; Vinters, H.V. Astrocytes: Biology and pathology. Acta Neuropathol., 2010, 119(1), 7-35.
[http://dx.doi.org/10.1007/s00401-009-0619-8] [PMID: 20012068]
[30]
Steliga, A. Kowiański, P.; Czuba, E.; Waśkow, M.; Moryś J.; Lietzau, G. Neurovascular unit as a source of ischemic stroke biomarkers—limitations of experimental studies and perspectives for clinical application. Transl. Stroke Res., 2020, 11(4), 553-579.
[http://dx.doi.org/10.1007/s12975-019-00744-5] [PMID: 31701356]
[31]
Winkler, A.; Wrzos, C.; Haberl, M.; Weil, M.T.; Gao, M.; Möbius, W.; Odoardi, F.; Thal, D.R.; Chang, M.; Opdenakker, G.; Bennett, J.L.; Nessler, S.; Stadelmann, C. Blood-brain barrier resealing in neuromyelitis optica occurs independently of astrocyte regeneration. J. Clin. Invest., 2021, 131(5), e141694.
[http://dx.doi.org/10.1172/JCI141694] [PMID: 33645550]
[32]
Rothhammer, V.; Quintana, F.J. Control of autoimmune CNS inflammation by astrocytes. Semin. Immunopathol., 2015, 37(6), 625-638.
[http://dx.doi.org/10.1007/s00281-015-0515-3] [PMID: 26223505]
[33]
Liddelow, S.A.; Guttenplan, K.A.; Clarke, L.E.; Bennett, F.C.; Bohlen, C.J.; Schirmer, L.; Bennett, M.L.; Münch, A.E.; Chung, W.S.; Peterson, T.C.; Wilton, D.K.; Frouin, A.; Napier, B.A.; Panicker, N.; Kumar, M.; Buckwalter, M.S.; Rowitch, D.H.; Dawson, V.L.; Dawson, T.M.; Stevens, B.; Barres, B.A. Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 2017, 541(7638), 481-487.
[http://dx.doi.org/10.1038/nature21029] [PMID: 28099414]
[34]
Pan, J.; Ma, N.; Zhong, J.; Yu, B.; Wan, J.; Zhang, W. Age-associated changes in microglia and astrocytes ameliorate blood-brain barrier dysfunction. Mol. Ther. Nucleic Acids, 2021, 26, 970-986.
[http://dx.doi.org/10.1016/j.omtn.2021.08.030] [PMID: 34760339]
[35]
Sweeney, M.D.; Ayyadurai, S.; Zlokovic, B.V. Pericytes of the neurovascular unit: Key functions and signaling pathways. Nat. Neurosci., 2016, 19(6), 771-783.
[http://dx.doi.org/10.1038/nn.4288] [PMID: 27227366]
[36]
Bhowmick, S.; D’Mello, V.; Caruso, D.; Wallerstein, A.; Abdul-Muneer, P.M. Impairment of pericyte-endothelium crosstalk leads to blood-brain barrier dysfunction following traumatic brain injury. Exp. Neurol., 2019, 317, 260-270.
[http://dx.doi.org/10.1016/j.expneurol.2019.03.014] [PMID: 30926390]
[37]
Daneman, R.; Prat, A. The blood-brain barrier. Cold Spring Harb. Perspect. Biol., 2015, 7(1), a020412.
[http://dx.doi.org/10.1101/cshperspect.a020412] [PMID: 25561720]
[38]
Stratman, A.N.; Malotte, K.M.; Mahan, R.D.; Davis, M.J.; Davis, G.E. Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. Blood, 2009, 114(24), 5091-5101.
[http://dx.doi.org/10.1182/blood-2009-05-222364] [PMID: 19822899]
[39]
Winkler, E.A.; Bell, R.D.; Zlokovic, B.V. Central nervous system pericytes in health and disease. Nat. Neurosci., 2011, 14(11), 1398-1405.
[http://dx.doi.org/10.1038/nn.2946] [PMID: 22030551]
[40]
Harris, A.L. Connexin channel permeability to cytoplasmic molecules. Prog. Biophys. Mol. Biol., 2007, 94(1-2), 120-143.
[http://dx.doi.org/10.1016/j.pbiomolbio.2007.03.011] [PMID: 17470375]
[41]
Yeh, H.; Ikezu, T. Transcriptional and epigenetic regulation of microglia in health and disease. Trends Mol. Med., 2019, 25(2), 96-111.
[http://dx.doi.org/10.1016/j.molmed.2018.11.004] [PMID: 30578089]
[42]
Nayak, D.; Roth, T.L.; McGavern, D.B. Microglia development and function. Annu. Rev. Immunol., 2014, 32(1), 367-402.
[http://dx.doi.org/10.1146/annurev-immunol-032713-120240] [PMID: 24471431]
[43]
Ginhoux, F.; Prinz, M. Origin of microglia: Current concepts and past controversies. Cold Spring Harb. Perspect. Biol., 2015, 7(8), a020537.
[http://dx.doi.org/10.1101/cshperspect.a020537] [PMID: 26134003]
[44]
Dai, X.M.; Ryan, G.R.; Hapel, A.J.; Dominguez, M.G.; Russell, R.G.; Kapp, S.; Sylvestre, V.; Stanley, E.R. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood, 2002, 99(1), 111-120.
[http://dx.doi.org/10.1182/blood.V99.1.111] [PMID: 11756160]
[45]
Sosna, J.; Philipp, S.; Albay, R., III; Reyes-Ruiz, J.M.; Baglietto-Vargas, D.; LaFerla, F.M.; Glabe, C.G. Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease. Mol. Neurodegener., 2018, 13(1), 11.
[http://dx.doi.org/10.1186/s13024-018-0244-x] [PMID: 29490706]
[46]
Satoh, J.; Kino, Y.; Asahina, N.; Takitani, M.; Miyoshi, J.; Ishida, T.; Saito, Y. TMEM119 marks a subset of microglia in the human brain. Neuropathology, 2016, 36(1), 39-49.
[http://dx.doi.org/10.1111/neup.12235] [PMID: 26250788]
[47]
Block, M.L.; Zecca, L.; Hong, J.S. Microglia-mediated neurotoxicity: Uncovering the molecular mechanisms. Nat. Rev. Neurosci., 2007, 8(1), 57-69.
[http://dx.doi.org/10.1038/nrn2038] [PMID: 17180163]
[48]
Gao, H.M.; Liu, B.; Zhang, W.; Hong, J.S. Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J., 2003, 17(13), 1-22.
[http://dx.doi.org/10.1096/fj.03-0109fje] [PMID: 12897068]
[49]
West, P.K.; McCorkindale, A.N.; Guennewig, B.; Ashhurst, T.M.; Viengkhou, B.; Hayashida, E.; Jung, S.R.; Butovsky, O.; Campbell, I.L.; Hofer, M.J. The cytokines interleukin-6 and interferon-α induce distinct microglia phenotypes. J. Neuroinflammation, 2022, 19(1), 96.
[http://dx.doi.org/10.1186/s12974-022-02441-x] [PMID: 35429976]
[50]
Ye, L.; Huang, Y.; Zhao, L.; Li, Y.; Sun, L.; Zhou, Y.; Qian, G.; Zheng, J.C. IL-1β and TNF-α induce neurotoxicity through glutamate production: A potential role for neuronal glutaminase. J. Neurochem., 2013, 125(6), 897-908.
[http://dx.doi.org/10.1111/jnc.12263] [PMID: 23578284]
[51]
Bernardino, L.; Xapelli, S.; Silva, A.P.; Jakobsen, B.; Poulsen, F.R.; Oliveira, C.R.; Vezzani, A.; Malva, J.O.; Zimmer, J. Modulator effects of interleukin-1beta and tumor necrosis factor-alpha on AMPA-induced excitotoxicity in mouse organotypic hippocampal slice cultures. J. Neurosci., 2005, 25(29), 6734-6744.
[http://dx.doi.org/10.1523/JNEUROSCI.1510-05.2005] [PMID: 16033883]
[52]
Masuch, A.; Shieh, C.H.; van Rooijen, N.; van Calker, D.; Biber, K. Mechanism of microglia neuroprotection: Involvement of P2X7, TNFα and valproic acid. Glia, 2016, 64(1), 76-89.
[http://dx.doi.org/10.1002/glia.22904] [PMID: 26295445]
[53]
Norden, D.M.; Fenn, A.M.; Dugan, A.; Godbout, J.P. TGFβ produced by IL-10 redirected astrocytes attenuates microglial activation. Glia, 2014, 62(6), 881-895.
[http://dx.doi.org/10.1002/glia.22647] [PMID: 24616125]
[54]
He, Y.; Gao, Y.; Zhang, Q.; Zhou, G.; Cao, F.; Yao, S. IL-4 switches microglia/macrophage M1/M2 polarization and alleviates neurological damage by modulating the JAK1/STAT6 pathway following ICH. Neuroscience, 2020, 437, 161-171.
[http://dx.doi.org/10.1016/j.neuroscience.2020.03.008] [PMID: 32224230]
[55]
Gordon, S.; Martinez, F.O. Alternative activation of macrophages: Mechanism and functions. Immunity, 2010, 32(5), 593-604.
[http://dx.doi.org/10.1016/j.immuni.2010.05.007] [PMID: 20510870]
[56]
Kobayashi, K.; Imagama, S.; Ohgomori, T.; Hirano, K.; Uchimura, K.; Sakamoto, K.; Hirakawa, A.; Takeuchi, H.; Suzumura, A.; Ishiguro, N.; Kadomatsu, K. Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis., 2013, 4(3), e525.
[http://dx.doi.org/10.1038/cddis.2013.54] [PMID: 23470532]
[57]
Sato, T.; Morita, I.; Sakaguchi, K.; Nakahama, K.I.; Smith, W.L.; Dewitt, D.L.; Murota, S.I. Involvement of prostaglandin endoperoxide H synthase-2 in osteoclast-like cell formation induced by interleukin-1β. J. Bone Miner. Res., 1996, 11(3), 392-400.
[http://dx.doi.org/10.1002/jbmr.5650110313] [PMID: 8852950]
[58]
Zhang, Y.; Feng, S.; Nie, K.; Li, Y.; Gao, Y.; Gan, R.; Wang, L.; Li, B.; Sun, X.; Wang, L.; Zhang, Y. TREM2 modulates microglia phenotypes in the neuroinflammation of Parkinson’s disease. Biochem. Biophys. Res. Commun., 2018, 499(4), 797-802.
[http://dx.doi.org/10.1016/j.bbrc.2018.03.226] [PMID: 29621548]
[59]
Edwards, D.N.; Bix, G.J. Roles of blood-brain barrier integrins and extracellular matrix in stroke. Am. J. Physiol. Cell Physiol., 2019, 316(2), C252-C263.
[http://dx.doi.org/10.1152/ajpcell.00151.2018] [PMID: 30462535]
[60]
Di Girolamo, N.; Indoh, I.; Jackson, N.; Wakefield, D.; McNeil, H.P.; Yan, W.; Geczy, C.; Arm, J.P.; Tedla, N. Human mast cell-derived gelatinase B (matrix metalloproteinase-9) is regulated by inflammatory cytokines: Role in cell migration. J. Immunol., 2006, 177(4), 2638-2650.
[http://dx.doi.org/10.4049/jimmunol.177.4.2638] [PMID: 16888026]
[61]
Li, S.Y.; Zhou, Y.L.; He, D.H.; Liu, W.; Fan, X.Z.; Wang, Q.; Pan, H.F.; Cheng, Y.X.; Liu, Y.Q. Centipeda minima extract exerts antineuroinflammatory effects via the inhibition of NF-κB signaling pathway. Phytomedicine, 2020, 67, 153164.
[http://dx.doi.org/10.1016/j.phymed.2019.153164] [PMID: 31954258]
[62]
Haruwaka, K.; Ikegami, A.; Tachibana, Y.; Ohno, N.; Konishi, H.; Hashimoto, A.; Matsumoto, M.; Kato, D.; Ono, R.; Kiyama, H.; Moorhouse, A.J.; Nabekura, J.; Wake, H. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat. Commun., 2019, 10(1), 5816.
[http://dx.doi.org/10.1038/s41467-019-13812-z] [PMID: 31862977]
[63]
Sarlus, H.; Heneka, M.T. Microglia in Alzheimer’s disease. J. Clin. Invest., 2017, 127(9), 3240-3249.
[http://dx.doi.org/10.1172/JCI90606] [PMID: 28862638]
[64]
Shaftel, S.S.; Kyrkanides, S.; Olschowka, J.A.; Miller, J.H.; Johnson, R.E.; O’Banion, M.K. Sustained hippocampal IL-1β overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J. Clin. Invest., 2007, 117(6), 1595-1604.
[http://dx.doi.org/10.1172/JCI31450] [PMID: 17549256]
[65]
Xiang, X.; Werner, G.; Bohrmann, B.; Liesz, A.; Mazaheri, F.; Capell, A.; Feederle, R.; Knuesel, I.; Kleinberger, G.; Haass, C. TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance. EMBO Mol. Med., 2016, 8(9), 992-1004.
[http://dx.doi.org/10.15252/emmm.201606370] [PMID: 27402340]
[66]
Martin, E.; Boucher, C.; Fontaine, B.; Delarasse, C. Distinct inflammatory phenotypes of microglia and monocyte-derived macrophages in Alzheimer’s disease models: effects of aging and amyloid pathology. Aging Cell, 2017, 16(1), 27-38.
[http://dx.doi.org/10.1111/acel.12522] [PMID: 27723233]
[67]
Jolivel, V.; Bicker, F.; Binamé, F.; Ploen, R.; Keller, S.; Gollan, R.; Jurek, B.; Birkenstock, J.; Poisa-Beiro, L.; Bruttger, J.; Opitz, V.; Thal, S.C.; Waisman, A.; Bäuerle, T.; Schäfer, M.K.; Zipp, F.; Schmidt, M.H.H. Perivascular microglia promote blood vessel disintegration in the ischemic penumbra. Acta Neuropathol., 2015, 129(2), 279-295.
[http://dx.doi.org/10.1007/s00401-014-1372-1] [PMID: 25500713]
[68]
Hong, S.; Beja-Glasser, V.F.; Nfonoyim, B.M.; Frouin, A.; Li, S.; Ramakrishnan, S.; Merry, K.M.; Shi, Q.; Rosenthal, A.; Barres, B.A.; Lemere, C.A.; Selkoe, D.J.; Stevens, B. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science, 2016, 352(6286), 712-716.
[http://dx.doi.org/10.1126/science.aad8373] [PMID: 27033548]
[69]
Wang, D.; Chen, F.; Han, Z.; Yin, Z.; Ge, X.; Lei, P. Relationship between amyloid-β deposition and blood–brain barrier dysfunction in Alzheimer’s Disease. Front. Cell. Neurosci., 2021, 15, 695479.
[http://dx.doi.org/10.3389/fncel.2021.695479] [PMID: 34349624]
[70]
Venegas, C.; Kumar, S.; Franklin, B.S.; Dierkes, T.; Brinkschulte, R.; Tejera, D.; Vieira-Saecker, A.; Schwartz, S.; Santarelli, F.; Kummer, M.P.; Griep, A.; Gelpi, E.; Beilharz, M.; Riedel, D.; Golenbock, D.T.; Geyer, M.; Walter, J.; Latz, E.; Heneka, M.T. Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease. Nature, 2017, 552(7685), 355-361.
[http://dx.doi.org/10.1038/nature25158] [PMID: 29293211]
[71]
Chen, A.Q.; Fang, Z.; Chen, X.L.; Yang, S.; Zhou, Y.F.; Mao, L.; Xia, Y.P.; Jin, H.J.; Li, Y.N.; You, M.F.; Wang, X.X.; Lei, H.; He, Q.W.; Hu, B. Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain–barrier disruption after ischemic stroke. Cell Death Dis., 2019, 10(7), 487.
[http://dx.doi.org/10.1038/s41419-019-1716-9] [PMID: 31221990]
[72]
Wong, D.; Dorovini-Zis, K.; Vincent, S.R. Cytokines, nitric oxide, and cGMP modulate the permeability of an in vitro model of the human blood–brain barrier. Exp. Neurol., 2004, 190(2), 446-455.
[http://dx.doi.org/10.1016/j.expneurol.2004.08.008] [PMID: 15530883]
[73]
Ruan, Z.; Zhang, D.; Huang, R.; Sun, W.; Hou, L.; Zhao, J.; Wang, Q. Microglial activation damages dopaminergic neurons through MMP-2/-9-mediated increase of blood-brain barrier permeability in a Parkinson’s Disease mouse model. Int. J. Mol. Sci., 2022, 23(5), 2793.
[http://dx.doi.org/10.3390/ijms23052793] [PMID: 35269933]
[74]
Haeren, R.H.L.; Rijkers, K.; Schijns, O.E.M.G.; Dings, J.; Hoogland, G.; van Zandvoort, M.A.M.J.; Vink, H.; van Overbeeke, J.J. In vivo assessment of the human cerebral microcirculation and its glycocalyx: A technical report. J. Neurosci. Methods, 2018, 303, 114-125.
[http://dx.doi.org/10.1016/j.jneumeth.2018.03.009] [PMID: 29578039]
[75]
Mulivor, A.W.; Lipowsky, H.H. Inflammation- and ischemia-induced shedding of venular glycocalyx. Am. J. Physiol. Heart Circ. Physiol., 2004, 286(5), H1672-H1680.
[http://dx.doi.org/10.1152/ajpheart.00832.2003] [PMID: 14704229]
[76]
Cancel, L.M.; Ebong, E.E.; Mensah, S.; Hirschberg, C.; Tarbell, J.M. Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model. Atherosclerosis, 2016, 252, 136-146.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.07.930] [PMID: 27529818]
[77]
Reinhold, A.K.; Rittner, H.L. Barrier function in the peripheral and central nervous system—a review. Pflugers Arch., 2017, 469(1), 123-134.
[http://dx.doi.org/10.1007/s00424-016-1920-8] [PMID: 27957611]
[78]
Zhang, J.; He, H.; Qiao, Y.; Zhou, T.; He, H.; Yi, S.; Zhang, L.; Mo, L.; Li, Y.; Jiang, W.; You, Z. Priming of microglia with IFN -γ impairs adult hippocampal neurogenesis and leads to depression-like behaviors and cognitive defects. Glia, 2020, 68(12), 2674-2692.
[http://dx.doi.org/10.1002/glia.23878] [PMID: 32652855]
[79]
Kawanokuchi, J.; Mizuno, T.; Takeuchi, H.; Kato, H.; Wang, J.; Mitsuma, N.; Suzumura, A. Production of interferon-γ by microglia. Mult. Scler., 2006, 12(5), 558-564.
[http://dx.doi.org/10.1177/1352458506070763] [PMID: 17086900]
[80]
Harcourt, B.H.; Sanchez, A.; Offermann, M.K. Ebola virus selectively inhibits responses to interferons, but not to interleukin-1beta, in endothelial cells. J. Virol., 1999, 73(4), 3491-3496.
[http://dx.doi.org/10.1128/JVI.73.4.3491-3496.1999] [PMID: 10074208]
[81]
Dietrich, J.B. The adhesion molecule ICAM-1 and its regulation in relation with the blood–brain barrier. J. Neuroimmunol., 2002, 128(1-2), 58-68.
[http://dx.doi.org/10.1016/S0165-5728(02)00114-5] [PMID: 12098511]
[82]
Miklossy, J.; Doudet, D.D.; Schwab, C.; Yu, S.; McGeer, E.G.; McGeer, P.L. Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys. Exp. Neurol., 2006, 197(2), 275-283.
[http://dx.doi.org/10.1016/j.expneurol.2005.10.034] [PMID: 16336966]
[83]
Werner, A.; Kloss, C.U.A.; Walter, J.; Kreutzberg, G.W.; Raivich, G. Intercellular adhesion molecule-1 (ICAM-1) in the mouse facial motor nucleus after axonal injury and during regeneration. J. Neurocytol., 1998, 27(4), 219-232.
[http://dx.doi.org/10.1023/A:1006928830251] [PMID: 10640181]
[84]
Kim, J.H.; Na, H.J.; Kim, C.K.; Kim, J.Y.; Ha, K.S.; Lee, H.; Chung, H.T.; Kwon, H.J.; Kwon, Y.G.; Kim, Y.M. The non-provitamin A carotenoid, lutein, inhibits NF-κB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-κB-inducing kinase pathways: Role of H2O2 in NF-κB activation. Free Radic. Biol. Med., 2008, 45(6), 885-896.
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.06.019] [PMID: 18620044]
[85]
Schreibelt, G.; Kooij, G.; Reijerkerk, A.; Doorn, R.; Gringhuis, S.I.; Pol, S.; Weksler, B.B.; Romero, I.A.; Couraud, P.O.; Piontek, J.; Blasig, I.E.; Dijkstra, C.D.; Ronken, E.; Vries, H.E. Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase, and PKB signaling. FASEB J., 2007, 21(13), 3666-3676.
[http://dx.doi.org/10.1096/fj.07-8329com] [PMID: 17586731]
[86]
Schreibelt, G.; Musters, R.J.P.; Reijerkerk, A.; de Groot, L.R.; van der Pol, S.M.A.; Hendrikx, E.M.L.; Döpp, E.D.; Dijkstra, C.D.; Drukarch, B.; de Vries, H.E. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. J. Immunol., 2006, 177(4), 2630-2637.
[http://dx.doi.org/10.4049/jimmunol.177.4.2630] [PMID: 16888025]
[87]
Kahles, T.; Luedike, P.; Endres, M.; Galla, H.J.; Steinmetz, H.; Busse, R.; Neumann-Haefelin, T.; Brandes, R.P. NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke, 2007, 38(11), 3000-3006.
[http://dx.doi.org/10.1161/STROKEAHA.107.489765] [PMID: 17916764]
[88]
Galasso, J.M.; Miller, M.J.; Cowell, R.M.; Harrison, J.K.; Warren, J.S.; Silverstein, F.S. Acute excitotoxic injury induces expression of monocyte chemoattractant protein-1 and its receptor, CCR2, in neonatal rat brain. Exp. Neurol., 2000, 165(2), 295-305.
[http://dx.doi.org/10.1006/exnr.2000.7466] [PMID: 10993690]
[89]
Wang, X.; Yue, T.L.; Barone, F.C.; Feuerstein, G.Z. Monocyte chemoattractant protein-1 messenger RNA expression in rat ischemic cortex. Stroke, 1995, 26(4), 661-666.
[http://dx.doi.org/10.1161/01.STR.26.4.661] [PMID: 7709415]
[90]
Ishizuka, K.; Kimura, T.; Igata-Yi, R.; Katsuragi, S.; Takamatsu, J.; Miyakawa, T. Identification of monocyte chemoattractant protein-1 in senile plaques and reactive microglia of Alzheimer’s disease. Psychiatry Clin. Neurosci., 1997, 51(3), 135-138.
[http://dx.doi.org/10.1111/j.1440-1819.1997.tb02375.x] [PMID: 9225377]
[91]
Jiang, Y.; Beller, D.I.; Frendl, G.; Graves, D.T. Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J. Immunol., 1992, 148(8), 2423-2428.
[http://dx.doi.org/10.4049/jimmunol.148.8.2423] [PMID: 1348518]
[92]
Stamatovic, S.M.; Shakui, P.; Keep, R.F.; Moore, B.B.; Kunkel, S.L.; Van Rooijen, N.; Andjelkovic, A.V. Monocyte chemoattractant protein-1 regulation of blood-brain barrier permeability. J. Cereb. Blood Flow Metab., 2005, 25(5), 593-606.
[http://dx.doi.org/10.1038/sj.jcbfm.9600055] [PMID: 15689955]
[93]
Dimitrijevic, O.B.; Stamatovic, S.M.; Keep, R.F.; Andjelkovic, A.V. Effects of the chemokine CCL2 on blood-brain barrier permeability during ischemia-reperfusion injury. J. Cereb. Blood Flow Metab., 2006, 26(6), 797-810.
[http://dx.doi.org/10.1038/sj.jcbfm.9600229] [PMID: 16192992]
[94]
Buffo, A.; Rolando, C.; Ceruti, S. Astrocytes in the damaged brain: Molecular and cellular insights into their reactive response and healing potential. Biochem. Pharmacol., 2010, 79(2), 77-89.
[http://dx.doi.org/10.1016/j.bcp.2009.09.014] [PMID: 19765548]
[95]
Lambertsen, K.L.; Meldgaard, M.; Ladeby, R.; Finsen, B. A quantitative study of microglial-macrophage synthesis of tumor necrosis factor during acute and late focal cerebral ischemia in mice. J. Cereb. Blood Flow Metab., 2005, 25(1), 119-135.
[http://dx.doi.org/10.1038/sj.jcbfm.9600014] [PMID: 15678118]
[96]
Holm, T.H.; Draeby, D.; Owens, T. Microglia are required for astroglial toll-like receptor 4 response and for optimal TLR2 and TLR3 response. Glia, 2012, 60(4), 630-638.
[http://dx.doi.org/10.1002/glia.22296] [PMID: 22271465]
[97]
Kirkley, K.S.; Popichak, K.A.; Afzali, M.F.; Legare, M.E.; Tjalkens, R.B. Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity. J. Neuroinflammation, 2017, 14(1), 99.
[http://dx.doi.org/10.1186/s12974-017-0871-0] [PMID: 28476157]
[98]
Ni, J.; Zhao, J.; Zhang, X.; Reinheckel, T.; Turk, V.; Nakanishi, H. Cathepsin H deficiency decreases hypoxia-ischemia-induced hippocampal atrophy in neonatal mice through attenuated TLR3/IFN-β signaling. J. Neuroinflammation, 2021, 18(1), 176.
[http://dx.doi.org/10.1186/s12974-021-02227-7] [PMID: 34376208]
[99]
VanRyzin, J.W.; Marquardt, A.E.; Argue, K.J.; Vecchiarelli, H.A.; Ashton, S.E.; Arambula, S.E.; Hill, M.N.; McCarthy, M.M. Microglial phagocytosis of newborn cells is induced by endocannabinoids and sculpts sex differences in juvenile rat social play. Neuron, 2019, 102(2), 435-449.e6.
[http://dx.doi.org/10.1016/j.neuron.2019.02.006] [PMID: 30827729]
[100]
Michinaga, S.; Koyama, Y. Dual roles of astrocyte-derived factors in regulation of blood-brain barrier function after brain damage. Int. J. Mol. Sci., 2019, 20(3), 571.
[http://dx.doi.org/10.3390/ijms20030571] [PMID: 30699952]
[101]
Jo, M.; Kim, J.H.; Song, G.J.; Seo, M.; Hwang, E.M.; Suk, K. Astrocytic Orosomucoid-2 modulates microglial activation and neuroinflammation. J. Neurosci., 2017, 37(11), 2878-2894.
[http://dx.doi.org/10.1523/JNEUROSCI.2534-16.2017] [PMID: 28193696]
[102]
Jang, E.; Lee, S.; Kim, J.H.; Kim, J.H.; Seo, J.W.; Lee, W.H.; Mori, K.; Nakao, K.; Suk, K. Secreted protein lipocalin-2 promotes microglial M1 polarization. FASEB J., 2013, 27(3), 1176-1190.
[http://dx.doi.org/10.1096/fj.12-222257] [PMID: 23207546]
[103]
Bi, F.; Huang, C.; Tong, J.; Qiu, G.; Huang, B.; Wu, Q.; Li, F.; Xu, Z.; Bowser, R.; Xia, X.G.; Zhou, H. Reactive astrocytes secrete lcn2 to promote neuron death. Proc. Natl. Acad. Sci. USA, 2013, 110(10), 4069-4074.
[http://dx.doi.org/10.1073/pnas.1218497110] [PMID: 23431168]
[104]
Rocha, S.M.; Cristovão, A.C.; Campos, F.L.; Fonseca, C.P.; Baltazar, G. Astrocyte-derived GDNF is a potent inhibitor of microglial activation. Neurobiol. Dis., 2012, 47(3), 407-415.
[http://dx.doi.org/10.1016/j.nbd.2012.04.014] [PMID: 22579772]
[105]
Tseng, K.Y.; Wu, J.S.; Chen, Y.H.; Airavaara, M.; Cheng, C.Y.; Ma, K.H. Modulating microglia/macrophage activation by CDNF promotes transplantation of fetal ventral mesencephalic graft survival and function in a hemiparkinsonian rat model. Biomedicines, 2022, 10(6), 1446.
[http://dx.doi.org/10.3390/biomedicines10061446] [PMID: 35740467]
[106]
Ding, H.; Chen, J.; Su, M.; Lin, Z.; Zhan, H.; Yang, F.; Li, W.; Xie, J.; Huang, Y.; Liu, X.; Liu, B.; Zhou, X. BDNF promotes activation of astrocytes and microglia contributing to neuroinflammation and mechanical allodynia in cyclophosphamide-induced cystitis. J. Neuroinflammation, 2020, 17(1), 19.
[http://dx.doi.org/10.1186/s12974-020-1704-0] [PMID: 31931832]
[107]
Tanuma, N.; Sakuma, H.; Sasaki, A.; Matsumoto, Y. Chemokine expression by astrocytes plays a role in microglia/macrophage activation and subsequent neurodegeneration in secondary progressive multiple sclerosis. Acta Neuropathol., 2006, 112(2), 195-204.
[http://dx.doi.org/10.1007/s00401-006-0083-7] [PMID: 16733654]
[108]
Docagne, F.; Nicole, O.; Gabriel, C.; Fernández-Monreal, M.; Lesné, S.; Ali, C.; Plawinski, L.; Carmeliet, P.; MacKenzie, E.T.; Buisson, A.; Vivien, D. Smad3-dependent induction of plasminogen activator inhibitor-1 in astrocytes mediates neuroprotective activity of transforming growth factor-beta 1 against NMDA-induced necrosis. Mol. Cell. Neurosci., 2002, 21(4), 634-644.
[http://dx.doi.org/10.1006/mcne.2002.1206] [PMID: 12504596]
[109]
Yang, L.; Niu, F.; Yao, H.; Liao, K.; Chen, X.; Kook, Y.; Ma, R.; Hu, G.; Buch, S. Exosomal miR-9 released from HIV Tat stimulated astrocytes mediates microglial migration. J. Neuroimmune Pharmacol., 2018, 13(3), 330-344.
[http://dx.doi.org/10.1007/s11481-018-9779-4] [PMID: 29497921]
[110]
Litvinchuk, A.; Wan, Y.W.; Swartzlander, D.B.; Chen, F.; Cole, A.; Propson, N.E.; Wang, Q.; Zhang, B.; Liu, Z.; Zheng, H. Complement C3aR inactivation attenuates tau pathology and reverses an immune network deregulated in tauopathy models and Alzheimer’s Disease. Neuron, 2018, 100(6), 1337-1353.e5.
[http://dx.doi.org/10.1016/j.neuron.2018.10.031] [PMID: 30415998]
[111]
Matsumoto, J.; Takata, F.; Machida, T.; Takahashi, H.; Soejima, Y.; Funakoshi, M.; Futagami, K.; Yamauchi, A.; Dohgu, S.; Kataoka, Y. Tumor necrosis factor-α-stimulated brain pericytes possess a unique cytokine and chemokine release profile and enhance microglial activation. Neurosci. Lett., 2014, 578, 133-138.
[http://dx.doi.org/10.1016/j.neulet.2014.06.052] [PMID: 24993300]
[112]
Dohgu, S.; Takata, F.; Matsumoto, J.; Kimura, I.; Yamauchi, A.; Kataoka, Y. Monomeric α-synuclein induces blood–brain barrier dysfunction through activated brain pericytes releasing inflammatory mediators in vitro. Microvasc. Res., 2019, 124, 61-66.
[http://dx.doi.org/10.1016/j.mvr.2019.03.005] [PMID: 30885616]
[113]
Matsumoto, J.; Dohgu, S.; Takata, F.; Machida, T. Bölükbaşi Hatip, F.F.; Hatip-Al-Khatib, I.; Yamauchi, A.; Kataoka, Y. TNF-α-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IκB-NFκB and JAK-STAT3 pathways. Brain Res., 2018, 1692, 34-44.
[http://dx.doi.org/10.1016/j.brainres.2018.04.023] [PMID: 29702085]
[114]
Rustenhoven, J.; Aalderink, M.; Scotter, E.L.; Oldfield, R.L.; Bergin, P.S.; Mee, E.W.; Graham, E.S.; Faull, R.L.M.; Curtis, M.A.; Park, T.I.H.; Dragunow, M. TGF-beta1 regulates human brain pericyte inflammatory processes involved in neurovasculature function. J. Neuroinflammation, 2016, 13(1), 37.
[http://dx.doi.org/10.1186/s12974-016-0503-0] [PMID: 26867675]
[115]
Perez, F.; Ruera, C.N.; Miculan, E.; Carasi, P.; Dubois-Camacho, K.; Garbi, L.; Guzman, L.; Hermoso, M.A.; Chirdo, F.G. IL-33 alarmin and its active proinflammatory fragments are released in small intestine in celiac disease. Front. Immunol., 2020, 11, 581445.
[http://dx.doi.org/10.3389/fimmu.2020.581445] [PMID: 33133101]
[116]
Fu, A.K.Y.; Hung, K.W.; Yuen, M.Y.F.; Zhou, X.; Mak, D.S.Y.; Chan, I.C.W.; Cheung, T.H.; Zhang, B.; Fu, W.Y.; Liew, F.Y.; Ip, N.Y. IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline. Proc. Natl. Acad. Sci. USA, 2016, 113(19), E2705-E2713.
[http://dx.doi.org/10.1073/pnas.1604032113] [PMID: 27091974]
[117]
Febinger, H.Y.; Thomasy, H.E.; Pavlova, M.N.; Ringgold, K.M.; Barf, P.R.; George, A.M.; Grillo, J.N.; Bachstetter, A.D.; Garcia, J.A.; Cardona, A.E.; Opp, M.R.; Gemma, C. Time-dependent effects of CX3CR1 in a mouse model of mild traumatic brain injury. J. Neuroinflammation, 2015, 12(1), 154.
[http://dx.doi.org/10.1186/s12974-015-0386-5] [PMID: 26329692]
[118]
Lee, C.Y.D.; Landreth, G.E. The role of microglia in amyloid clearance from the AD brain. J. Neural Transm. (Vienna), 2010, 117(8), 949-960.
[http://dx.doi.org/10.1007/s00702-010-0433-4] [PMID: 20552234]
[119]
Prinz, M.; Priller, J. Tickets to the brain: Role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. J. Neuroimmunol., 2010, 224(1-2), 80-84.
[http://dx.doi.org/10.1016/j.jneuroim.2010.05.015] [PMID: 20554025]
[120]
Lauro, C.; Catalano, M.; Trettel, F.; Limatola, C. Fractalkine in the nervous system: Neuroprotective or neurotoxic molecule? Ann. N. Y. Acad. Sci., 2015, 1351(1), 141-148.
[http://dx.doi.org/10.1111/nyas.12805] [PMID: 26084002]
[121]
Tai, Y.F.; Pavese, N.; Gerhard, A.; Tabrizi, S.J.; Barker, R.A.; Brooks, D.J.; Piccini, P. Microglial activation in presymptomatic Huntington’s disease gene carriers. Brain, 2007, 130(7), 1759-1766.
[http://dx.doi.org/10.1093/brain/awm044] [PMID: 17400599]
[122]
Miller, J.P.; Holcomb, J.; Al-Ramahi, I.; de Haro, M.; Gafni, J.; Zhang, N.; Kim, E.; Sanhueza, M.; Torcassi, C.; Kwak, S.; Botas, J.; Hughes, R.E.; Ellerby, L.M. Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington’s disease. Neuron, 2010, 67(2), 199-212.
[http://dx.doi.org/10.1016/j.neuron.2010.06.021] [PMID: 20670829]
[123]
Kim, Y.S.; Kim, S.S.; Cho, J.J.; Choi, D.H.; Hwang, O.; Shin, D.H.; Chun, H.S.; Beal, M.F.; Joh, T.H. Matrix metalloproteinase-3: A novel signaling proteinase from apoptotic neuronal cells that activates microglia. J. Neurosci., 2005, 25(14), 3701-3711.
[http://dx.doi.org/10.1523/JNEUROSCI.4346-04.2005] [PMID: 15814801]
[124]
Ryu, J.K.; Cho, T.; Choi, H.B.; Wang, Y.T.; McLarnon, J.G. Microglial VEGF receptor response is an integral chemotactic component in Alzheimer’s disease pathology. J. Neurosci., 2009, 29(1), 3-13.
[http://dx.doi.org/10.1523/JNEUROSCI.2888-08.2009] [PMID: 19129379]
[125]
Issa, R.; Krupinski, J.; Bujny, T.; Kumar, S.; Kaluza, J.; Kumar, P. Vascular endothelial growth factor and its receptor, KDR, in human brain tissue after ischemic stroke. Lab. Invest., 1999, 79(4), 417-425.
[PMID: 10211994]
[126]
Schoknecht, K.; Shalev, H. Blood-brain barrier dysfunction in brain diseases: Clinical experience. Epilepsia, 2012, 53(Suppl. 6), 7-13.
[http://dx.doi.org/10.1111/j.1528-1167.2012.03697.x] [PMID: 23134490]
[127]
Xu, Z.; Han, K.; Chen, J.; Wang, C.; Dong, Y.; Yu, M.; Bai, R.; Huang, C.; Hou, L. Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia. J. Neurochem., 2017, 142(5), 700-709.
[http://dx.doi.org/10.1111/jnc.14108] [PMID: 28632969]
[128]
Xu, L.; He, D.; Bai, Y. Microglia-mediated inflammation and neurodegenerative disease. Mol. Neurobiol., 2016, 53(10), 6709-6715.
[http://dx.doi.org/10.1007/s12035-015-9593-4] [PMID: 26659872]

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