Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

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

Review Article

Crosstalk between Microglia and Neurons in Neurotrauma: An Overview of the Underlying Mechanisms

Author(s): Muhammad Ali Haidar, Stanley Ibeh, Zaynab Shakkour, Mohammad Amine Reslan, Judith Nwaiwu, Yomna Adel Moqidem, Georgio Sader, Rachel G. Nickles, Ismail Babale, Aneese A. Jaffa, Mohamed Salama, Abdullah Shaito* and Firas Kobeissy*

Volume 20, Issue 11, 2022

Published on: 19 April, 2022

Page: [2050 - 2065] Pages: 16

DOI: 10.2174/1570159X19666211202123322

Price: $65

Abstract

Microglia are the resident immune cells of the brain and play a crucial role in housekeeping and maintaining homeostasis of the brain microenvironment. Upon injury or disease, microglial cells become activated, at least partly, via signals initiated by injured neurons. Activated microglia, thereby, contribute to both neuroprotection and neuroinflammation. However, sustained microglial activation initiates a chronic neuroinflammatory response which can disturb neuronal health and disrupt communications between neurons and microglia. Thus, microglia-neuron crosstalk is critical in a healthy brain as well as during states of injury or disease. As most studies focus on how neurons and microglia act in isolation during neurotrauma, there is a need to understand the interplay between these cells in brain pathophysiology. This review highlights how neurons and microglia reciprocally communicate under physiological conditions and during brain injury and disease. Furthermore, the modes of microglia-neuron communication are exposed, focusing on cell-contact dependent signaling and communication by the secretion of soluble factors like cytokines and growth factors. In addition, it has been discussed that how microglia-neuron interactions could exert either beneficial neurotrophic effects or pathologic proinflammatory responses. We further explore how aberrations in microglia-neuron crosstalk may be involved in central nervous system (CNS) anomalies, namely traumatic brain injury (TBI), neurodegeneration, and ischemic stroke. A clear understanding of how the microglia-neuron crosstalk contributes to the pathogenesis of brain pathologies may offer novel therapeutic avenues of brain trauma treatment.

Keywords: CNS Injury, microglia-neuron interaction, cellular crosstalk, neuroinflammation, microglial activation, microglia phenotypes.

Graphical Abstract

[1]
Olah, M.; Biber, K.; Vinet, J.; Boddeke, H.W. Microglia phenotype diversity. CNS Neurol. Disord. Drug Targets, 2011, 10(1), 108-118.
[http://dx.doi.org/10.2174/187152711794488575] [PMID: 21143141]
[2]
Muoio, V.; Persson, P.B.; Sendeski, M.M. The neurovascular unit - concept review. Acta Physiol. (Oxf.), 2014, 210(4), 790-798.
[http://dx.doi.org/10.1111/apha.12250] [PMID: 24629161]
[3]
Weiss, N.; Miller, F.; Cazaubon, S.; Couraud, P-O. The blood-brain barrier in brain homeostasis and neurological diseases. Biochim. Biophys. Acta, 2009, 1788(4), 842-857.
[http://dx.doi.org/10.1016/j.bbamem.2008.10.022] [PMID: 19061857]
[4]
Mayer, C.L.; Huber, B.R.; Peskind, E. Traumatic brain injury, neuroinflammation, and post-traumatic headaches. Headache, 2013, 53(9), 1523-1530.
[http://dx.doi.org/10.1111/head.12173] [PMID: 24090534]
[5]
Donat, C.K.; Scott, G.; Gentleman, S.M.; Sastre, M. Microglial activation in traumatic brain injury. Front. Aging Neurosci., 2017, 9, 208.
[http://dx.doi.org/10.3389/fnagi.2017.00208] [PMID: 28701948]
[6]
Szepesi, Z.; Manouchehrian, O.; Bachiller, S.; Deierborg, T. Bidirectional microglia-neuron communication in health and disease. Front. Cell. Neurosci., 2018, 12(323), 323.
[http://dx.doi.org/10.3389/fncel.2018.00323] [PMID: 30319362]
[7]
Pósfai, B.; Cserép, C.; Orsolits, B.; Dénes, Á. New insights into microglia-neuron interactions: a neuron’s perspective. Neuroscience, 2019, 405, 103-117.
[http://dx.doi.org/10.1016/j.neuroscience.2018.04.046] [PMID: 29753862]
[8]
Kumar, A.; Loane, D.J. Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behav. Immun., 2012, 26(8), 1191-1201.
[http://dx.doi.org/10.1016/j.bbi.2012.06.008] [PMID: 22728326]
[9]
Ritzel, R.M.; Li, Y.; He, J.; Khan, N.; Doran, S.J.; Faden, A.I.; Wu, J. Sustained neuronal and microglial alterations are associated with diverse neurobehavioral dysfunction long after experimental brain injury. Neurobiol. Dis., 2020, 136, 104713.
[http://dx.doi.org/10.1016/j.nbd.2019.104713] [PMID: 31843705]
[10]
Shinozaki, Y.; Shibata, K.; Yoshida, K.; Shigetomi, E.; Gachet, C.; Ikenaka, K.; Tanaka, K.F.; Koizumi, S. Transformation of astrocytes to a neuroprotective phenotype by microglia via P2Y1 receptor downregulation. Cell Rep., 2017, 19(6), 1151-1164.
[http://dx.doi.org/10.1016/j.celrep.2017.04.047] [PMID: 28494865]
[11]
Fang, K-M.; Yang, C-S.; Sun, S.H.; Tzeng, S-F. Microglial phagocytosis attenuated by short-term exposure to exogenous ATP through P2X receptor action. J. Neurochem., 2009, 111(5), 1225-1237.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06409.x] [PMID: 19860838]
[12]
Dinet, V.; Petry, K.G.; Badaut, J. Brain-immune interactions and neuroinflammation after traumatic brain injury. Front. Neurosci., 2019, 13, 1178.
[http://dx.doi.org/10.3389/fnins.2019.01178] [PMID: 31780883]
[13]
Ransohoff, R.M.; Cardona, A.E. The myeloid cells of the central nervous system parenchyma. Nature, 2010, 468(7321), 253-262.
[http://dx.doi.org/10.1038/nature09615] [PMID: 21068834]
[14]
Hernangómez, M.; Mestre, L.; Correa, F.G.; Loría, F.; Mecha, M.; Iñigo, P.M.; Docagne, F.; Williams, R.O.; Borrell, J.; Guaza, C. CD200-CD200R1 interaction contributes to neuroprotective effects of anandamide on experimentally induced inflammation. Glia, 2012, 60(9), 1437-1450.
[http://dx.doi.org/10.1002/glia.22366] [PMID: 22653796]
[15]
Kreutzberg, G.W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci., 1996, 19(8), 312-318.
[http://dx.doi.org/10.1016/0166-2236(96)10049-7] [PMID: 8843599]
[16]
McPherson, C.A.; Merrick, B.A.; Harry, G.J. In vivo molecular markers for pro-inflammatory cytokine M1 stage and resident microglia in trimethyltin-induced hippocampal injury. Neurotox. Res., 2014, 25(1), 45-56.
[http://dx.doi.org/10.1007/s12640-013-9422-3] [PMID: 24002884]
[17]
Ransohoff, R.M.; Brown, M.A. Innate immunity in the central nervous system. J. Clin. Invest., 2012, 122(4), 1164-1171.
[http://dx.doi.org/10.1172/JCI58644] [PMID: 22466658]
[18]
David, S.; Kroner, A.; Greenhalgh, A.D.; Zarruk, J.G.; López-Vales, R. Myeloid cell responses after spinal cord injury. J. Neuroimmunol., 2018, 321, 97-108.
[http://dx.doi.org/10.1016/j.jneuroim.2018.06.003] [PMID: 29957394]
[19]
Filiano, A.J.; Gadani, S.P.; Kipnis, J. How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat. Rev. Neurosci., 2017, 18(6), 375-384.
[http://dx.doi.org/10.1038/nrn.2017.39] [PMID: 28446786]
[20]
Kierdorf, K.; Prinz, M. Microglia in steady state. J. Clin. Invest., 2017, 127(9), 3201-3209.
[http://dx.doi.org/10.1172/JCI90602] [PMID: 28714861]
[21]
Butovsky, O.; Jedrychowski, M.P.; Moore, C.S.; Cialic, R.; Lanser, A.J.; Gabriely, G.; Koeglsperger, T.; Dake, B.; Wu, P.M.; Doykan, C.E.; Fanek, Z.; Liu, L.; Chen, Z.; Rothstein, J.D.; Ransohoff, R.M.; Gygi, S.P.; Antel, J.P.; Weiner, H.L. Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat. Neurosci., 2014, 17(1), 131-143.
[http://dx.doi.org/10.1038/nn.3599] [PMID: 24316888]
[22]
Habib, P.; Slowik, A.; Zendedel, A.; Johann, S.; Dang, J.; Beyer, C. Regulation of hypoxia-induced inflammatory responses and M1-M2 phenotype switch of primary rat microglia by sex steroids. J. Mol. Neurosci., 2014, 52(2), 277-285.
[http://dx.doi.org/10.1007/s12031-013-0137-y] [PMID: 24163150]
[23]
Yao, X.; Liu, S.; Ding, W.; Yue, P.; Jiang, Q.; Zhao, M.; Hu, F.; Zhang, H. TLR4 signal ablation attenuated neurological deficits by regulat-ing microglial M1/M2 phenotype after traumatic brain injury in mice. J. Neuroimmunol., 2017, 310, 38-45.
[http://dx.doi.org/10.1016/j.jneuroim.2017.06.006] [PMID: 28778443]
[24]
Arcuri, C.; Mecca, C.; Bianchi, R.; Giambanco, I.; Donato, R. The pathophysiological role of microglia in dynamic surveillance, phagocy-tosis and structural remodeling of the developing CNS. Front. Mol. Neurosci., 2017, 10, 191.
[http://dx.doi.org/10.3389/fnmol.2017.00191] [PMID: 28674485]
[25]
Essandoh, K.; Li, Y.; Huo, J.; Fan, G-C. MiRNA-mediated macrophage polarization and its potential role in the regulation of inflammatory response. Shock, 2016, 46(2), 122-131.
[http://dx.doi.org/10.1097/SHK.0000000000000604] [PMID: 26954942]
[26]
Orihuela, R.; McPherson, C.A.; Harry, G.J. Microglial M1/M2 polarization and metabolic states. Br. J. Pharmacol., 2016, 173(4), 649-665.
[http://dx.doi.org/10.1111/bph.13139] [PMID: 25800044]
[27]
Tang, Y.; Le, W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol. Neurobiol., 2016, 53(2), 1181-1194.
[http://dx.doi.org/10.1007/s12035-014-9070-5] [PMID: 25598354]
[28]
Colton, C.A. Heterogeneity of microglial activation in the innate immune response in the brain. J. Neuroimmune Pharmacol., 2009, 4(4), 399-418.
[http://dx.doi.org/10.1007/s11481-009-9164-4] [PMID: 19655259]
[29]
Norden, D.M.; Trojanowski, P.J.; Villanueva, E.; Navarro, E.; Godbout, J.P. Sequential activation of microglia and astrocyte cytokine ex-pression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge. Glia, 2016, 64(2), 300-316.
[http://dx.doi.org/10.1002/glia.22930] [PMID: 26470014]
[30]
Sica, A.; Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest., 2012, 122(3), 787-795.
[http://dx.doi.org/10.1172/JCI59643] [PMID: 22378047]
[31]
Graeber, M.B. Changing face of microglia. Science, 2010, 330(6005), 783-788.
[http://dx.doi.org/10.1126/science.1190929] [PMID: 21051630]
[32]
Beins, E.; Ulas, T.; Ternes, S.; Neumann, H.; Schultze, J.L.; Zimmer, A. Characterization of inflammatory markers and transcriptome pro-files of differentially activated embryonic stem cell-derived microglia. Glia, 2016, 64(6), 1007-1020.
[http://dx.doi.org/10.1002/glia.22979] [PMID: 26959607]
[33]
Laffer, B.; Bauer, D.; Wasmuth, S.; Busch, M.; Jalilvand, T.V.; Thanos, S.; Hörste, G.M.Z.; Loser, K.; Langmann, T.; Heiligenhaus, A.; Kasper, M. Loss of IL-10 promotes differentiation of microglia to a M1 phenotype. Front. Cell. Neurosci., 2019, 13, 430.
[http://dx.doi.org/10.3389/fncel.2019.00430] [PMID: 31649508]
[34]
Hammond, T.R.; Dufort, C.; Dissing-Olesen, L.; Giera, S.; Young, A.; Wysoker, A.; Walker, A.J.; Gergits, F.; Segel, M.; Nemesh, J.; Marsh, S.E.; Saunders, A.; Macosko, E.; Ginhoux, F.; Chen, J.; Franklin, R.J.M.; Piao, X.; McCarroll, S.A.; Stevens, B. Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity, 2019, 50(1), 253-271.e6.
[http://dx.doi.org/10.1016/j.immuni.2018.11.004] [PMID: 30471926]
[35]
Liu, B.; Wang, K.; Gao, H.M.; Mandavilli, B.; Wang, J.Y.; Hong, J.S. Molecular consequences of activated microglia in the brain: overacti-vation induces apoptosis. J. Neurochem., 2001, 77(1), 182-189.
[http://dx.doi.org/10.1046/j.1471-4159.2001.t01-1-00216.x] [PMID: 11279274]
[36]
Ghosh, M.; Xu, Y.; Pearse, D.D. Cyclic AMP is a key regulator of M1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines. J. Neuroinflammation, 2016, 13(1), 9.
[http://dx.doi.org/10.1186/s12974-015-0463-9] [PMID: 26757726]
[37]
Almolda, B.; de Labra, C.; Barrera, I.; Gruart, A.; Delgado-Garcia, J.M.; Villacampa, N.; Vilella, A.; Hofer, M.J.; Hidalgo, J.; Campbell, I.L.; González, B. Alterations in microglial phenotype and hippocampal neuronal function in transgenic mice with astrocyte-targeted pro-duction of interleukin-10. Brain Behav. Immun., 2015, 45, 80-97.
[38]
Gordon, S. Alternative activation of macrophages. Nat. Rev. Immunol., 2003, 3(1), 23-35.
[http://dx.doi.org/10.1038/nri978] [PMID: 12511873]
[39]
Lisi, L.; Stigliano, E.; Lauriola, L.; Navarra, P.; Dello Russo, C. Proinflammatory-activated glioma cells induce a switch in microglial polar-ization and activation status, from a predominant M2b phenotype to a mixture of M1 and M2a/B polarized cells. ASN Neuro, 2014, 6(3), 171-183.
[http://dx.doi.org/10.1042/AN20130045] [PMID: 24689533]
[40]
Chhor, V.; Charpentier, T.L.; Lebon, S.; Oré, M. -.V.; Celador, I.L.; Josserand, J.; Degos, V.; Jacotot, E.; Hagberg, H.; Sävman, K.; Mallard, C.; Gressens, P.; Fleiss, B. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain Behav. Immun., 2013, 32, 70-85.
[http://dx.doi.org/10.1016/j.bbi.2013.02.005] [PMID: 23454862]
[41]
Richard, M. Ransohoff VHP. Microglial physiology: unique stimuli, specialized responses. Annu. Rev. Immunol., 2009, 27, 119-145.
[42]
Taylor, S.E.; Morganti-Kossmann, C.; Lifshitz, J.; Ziebell, J.M. Rod microglia: a morphological definition. PLoS One, 2014, 9(5), e97096.
[http://dx.doi.org/10.1371/journal.pone.0097096] [PMID: 24830807]
[43]
Morrison, H.; Young, K.; Qureshi, M.; Rowe, R.K.; Lifshitz, J. Quantitative microglia analyses reveal diverse morphologic responses in the rat cortex after diffuse brain injury. Sci. Rep., 2017, 7(1), 13211.
[http://dx.doi.org/10.1038/s41598-017-13581-z] [PMID: 29038483]
[44]
Perry, V.H.; O’Connor, V. The role of microglia in synaptic stripping and synaptic degeneration: a revised perspective. ASN Neuro, 2010, 2(5), e00047.
[http://dx.doi.org/10.1042/AN20100024] [PMID: 20967131]
[45]
Ziebell, J.M.; Taylor, S.E.; Cao, T.; Harrison, J.L.; Lifshitz, J. Rod microglia: elongation, alignment, and coupling to form trains across the somatosensory cortex after experimental diffuse brain injury. J. Neuroinflammation, 2012, 9(1), 247.
[http://dx.doi.org/10.1186/1742-2094-9-247] [PMID: 23111107]
[46]
Cho, B.P.; Song, D.Y.; Sugama, S.; Shin, D.H.; Shimizu, Y.; Kim, S.S.; Kim, Y.S.; Joh, T.H. Pathological dynamics of activated microglia following medial forebrain bundle transection. Glia, 2006, 53(1), 92-102.
[http://dx.doi.org/10.1002/glia.20265] [PMID: 16206155]
[47]
Wu, S.; Nguyen, L.T.M.; Pan, H.; Hassan, S.; Dai, Y.; Xu, J.; Wen, Z. Two phenotypically and functionally distinct microglial populations in adult zebrafish. Sci. Adv., 2020, 6(47), eabd1160.
[http://dx.doi.org/10.1126/sciadv.abd1160] [PMID: 33208372]
[48]
Uriarte Huarte, O.; Richart, L.; Mittelbronn, M.; Michelucci, A. Microglia in health and disease: the strength to be diverse and reactive. Front. Cell. Neurosci., 2021, 15, 660523.
[http://dx.doi.org/10.3389/fncel.2021.660523] [PMID: 33867943]
[49]
Geirsdottir, L.; David, E.; Keren-Shaul, H.; Weiner, A.; Bohlen, S.C.; Neuber, J.; Balic, A.; Giladi, A.; Sheban, F.; Dutertre, C.A.; Pfeifle, C.; Peri, F.; Raffo-Romero, A.; Vizioli, J.; Matiasek, K.; Scheiwe, C.; Meckel, S.; Mätz-Rensing, K.; van der Meer, F.; Thormodsson, F.R.; Stadelmann, C.; Zilkha, N.; Kimchi, T.; Ginhoux, F.; Ulitsky, I.; Erny, D.; Amit, I.; Prinz, M. Cross-species single-cell analysis reveals di-vergence of the primate microglia program. Cell, 2019, 179(7), 1609-1622.e16.
[http://dx.doi.org/10.1016/j.cell.2019.11.010] [PMID: 31835035]
[50]
Ochocka, N.; Kaminska, B. Microglia diversity in healthy and diseased brain: insights from single-cell omics. Int. J. Mol. Sci., 2021, 22(6), 3027.
[http://dx.doi.org/10.3390/ijms22063027] [PMID: 33809675]
[51]
Subramaniam, S.R.; Federoff, H.J. Targeting microglial activation states as a therapeutic avenue in Parkinson’s disease. Front. Aging Neurosci., 2017, 9, 176.
[http://dx.doi.org/10.3389/fnagi.2017.00176] [PMID: 28642697]
[52]
Liu, H.; Leak, R.K.; Hu, X. Neurotransmitter receptors on microglia. Stroke Vasc. Neurol., 2016, 1(2), 52-58.
[http://dx.doi.org/10.1136/svn-2016-000012] [PMID: 28959464]
[53]
Davalos, D.; Grutzendler, J.; Yang, G.; Kim, J.V.; Zuo, Y.; Jung, S.; Littman, D.R.; Dustin, M.L.; Gan, W.B. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci., 2005, 8(6), 752-758.
[http://dx.doi.org/10.1038/nn1472] [PMID: 15895084]
[54]
Tian, L.; Ma, L.; Kaarela, T.; Li, Z. Neuroimmune crosstalk in the central nervous system and its significance for neurological diseases. J. Neuroinflammation, 2012, 9(1), 155.
[http://dx.doi.org/10.1186/1742-2094-9-155] [PMID: 22747919]
[55]
Mondello, S.; Thelin, E.P.; Shaw, G.; Salzet, M.; Visalli, C.; Cizkova, D.; Kobeissy, F.; Buki, A. Extracellular vesicles: pathogenetic, diag-nostic and therapeutic value in traumatic brain injury. Expert Rev. Proteomics, 2018, 15(5), 451-461.
[http://dx.doi.org/10.1080/14789450.2018.1464914] [PMID: 29671356]
[56]
Paolicelli, R.C.; Bergamini, G.; Rajendran, L. Cell-to-cell communication by extracellular vesicles: focus on microglia. Neuroscience, 2019, 405, 148-157.
[http://dx.doi.org/10.1016/j.neuroscience.2018.04.003] [PMID: 29660443]
[57]
Budnik, V.; Ruiz-Cañada, C.; Wendler, F. Extracellular vesicles round off communication in the nervous system. Nat. Rev. Neurosci., 2016, 17(3), 160-172.
[http://dx.doi.org/10.1038/nrn.2015.29] [PMID: 26891626]
[58]
Krämer-Albers, E.M.; Hill, A.F. Extracellular vesicles: interneural shuttles of complex messages. Curr. Opin. Neurobiol., 2016, 39, 101-107.
[http://dx.doi.org/10.1016/j.conb.2016.04.016] [PMID: 27183381]
[59]
Frühbeis, C.; Fröhlich, D.; Kuo, W.P.; Krämer-Albers, E.M. Extracellular vesicles as mediators of neuron-glia communication. Front. Cell. Neurosci., 2013, 7, 182.
[http://dx.doi.org/10.3389/fncel.2013.00182] [PMID: 24194697]
[60]
Antonucci, F.; Turola, E.; Riganti, L.; Caleo, M.; Gabrielli, M.; Perrotta, C.; Novellino, L.; Clementi, E.; Giussani, P.; Viani, P.; Matteoli, M.; Verderio, C. Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism. EMBO J., 2012, 31(5), 1231-1240.
[http://dx.doi.org/10.1038/emboj.2011.489] [PMID: 22246184]
[61]
Rajendran, L.; Honsho, M.; Zahn, T.R.; Keller, P.; Geiger, K.D.; Verkade, P.; Simons, K. Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. USA, 2006, 103(30), 11172-11177.
[http://dx.doi.org/10.1073/pnas.0603838103] [PMID: 16837572]
[62]
Vilette, D.; Courte, J.; Peyrin, J.M.; Coudert, L.; Schaeffer, L.; Andréoletti, O.; Leblanc, P. Cellular mechanisms responsible for cell-to-cell spreading of prions. Cell. Mol. Life Sci., 2018, 75(14), 2557-2574.
[http://dx.doi.org/10.1007/s00018-018-2823-y] [PMID: 29761205]
[63]
Chugh, D.; Ekdahl, C.T. Interactions between microglia and newly formed hippocampal neurons in physiological and seizure-induced inflammatory environment. Brain Plast., 2016, 1(2), 215-221.
[http://dx.doi.org/10.3233/BPL-150014] [PMID: 29765843]
[64]
Baalman, K.; Marin, M.A.; Ho, T.S.; Godoy, M.; Cherian, L.; Robertson, C.; Rasband, M.N. Axon initial segment-associated microglia. J. Neurosci., 2015, 35(5), 2283-2292.
[http://dx.doi.org/10.1523/JNEUROSCI.3751-14.2015] [PMID: 25653382]
[65]
Cserép, C.; Pósfai, B.; Lénárt, N.; Fekete, R.; László, Z.I.; Lele, Z.; Orsolits, B.; Molnár, G.; Heindl, S.; Schwarcz, A.D.; Ujvári, K.; Környei, Z.; Tóth, K.; Szabadits, E.; Sperlágh, B.; Baranyi, M.; Csiba, L.; Hortobágyi, T.; Maglóczky, Z.; Martinecz, B.; Szabó, G.; Erdélyi, F. Szipőcs, R.; Tamkun, M.M.; Gesierich, B.; Duering, M.; Katona, I.; Liesz, A.; Tamás, G.; Dénes, Á. Microglia monitor and protect neu-ronal function through specialized somatic purinergic junctions. Science, 2020, 367(6477), 528-537.
[http://dx.doi.org/10.1126/science.aax6752] [PMID: 31831638]
[66]
Schafer, D.P.; Lehrman, E.K.; Kautzman, A.G.; Koyama, R.; Mardinly, A.R.; Yamasaki, R.; Ransohoff, R.M.; Greenberg, M.E.; Barres, B.A.; Stevens, B. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron, 2012, 74(4), 691-705.
[http://dx.doi.org/10.1016/j.neuron.2012.03.026] [PMID: 22632727]
[67]
Paolicelli, R.C.; Bolasco, G.; Pagani, F.; Maggi, L.; Scianni, M.; Panzanelli, P.; Giustetto, M.; Ferreira, T.A.; Guiducci, E.; Dumas, L.; Ragozzino, D.; Gross, C.T. Synaptic pruning by microglia is necessary for normal brain development. Science, 2011, 333(6048), 1456-1458.
[http://dx.doi.org/10.1126/science.1202529] [PMID: 21778362]
[68]
Wu, Y.; Dissing-Olesen, L.; MacVicar, B.A.; Stevens, B. Microglia: dynamic mediators of synapse development and plasticity. Trends Immunol., 2015, 36(10), 605-613.
[http://dx.doi.org/10.1016/j.it.2015.08.008] [PMID: 26431938]
[69]
Harrison, J.K.; Jiang, Y.; Chen, S.; Xia, Y.; Maciejewski, D.; McNamara, R.K.; Streit, W.J.; Salafranca, M.N.; Adhikari, S.; Thompson, D.A.; Botti, P.; Bacon, K.B.; Feng, L. Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc. Natl. Acad. Sci. USA, 1998, 95(18), 10896-10901.
[http://dx.doi.org/10.1073/pnas.95.18.10896] [PMID: 9724801]
[70]
Ransohoff, R.M.; Stevens, B. Neuroscience. How many cell types does it take to wire a brain? Science, 2011, 333(6048), 1391-1392.
[http://dx.doi.org/10.1126/science.1212112] [PMID: 21903801]
[71]
Sakai, J. Core Concept: How synaptic pruning shapes neural wiring during development and, possibly, in disease. Proc. Natl. Acad. Sci. USA, 2020, 117(28), 16096-16099.
[http://dx.doi.org/10.1073/pnas.2010281117] [PMID: 32581125]
[72]
Zhan, Y.; Paolicelli, R.C.; Sforazzini, F.; Weinhard, L.; Bolasco, G.; Pagani, F.; Vyssotski, A.L.; Bifone, A.; Gozzi, A.; Ragozzino, D.; Gross, C.T. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat. Neurosci., 2014, 17(3), 400-406.
[http://dx.doi.org/10.1038/nn.3641] [PMID: 24487234]
[73]
Nimmerjahn, A.; Kirchhoff, F.; Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science, 2005, 308(5726), 1314-1318.
[http://dx.doi.org/10.1126/science.1110647] [PMID: 15831717]
[74]
Stevens, B.; Allen, N.J.; Vazquez, L.E.; Howell, G.R.; Christopherson, K.S.; Nouri, N.; Micheva, K.D.; Mehalow, A.K.; Huberman, A.D.; Stafford, B.; Sher, A.; Litke, A.M.; Lambris, J.D.; Smith, S.J.; John, S.W.; Barres, B.A. The classical complement cascade mediates CNS synapse elimination. Cell, 2007, 131(6), 1164-1178.
[http://dx.doi.org/10.1016/j.cell.2007.10.036] [PMID: 18083105]
[75]
Scott-Hewitt, N.; Perrucci, F.; Morini, R.; Erreni, M.; Mahoney, M.; Witkowska, A.; Carey, A.; Faggiani, E.; Schuetz, L.T.; Mason, S.; Tamborini, M.; Bizzotto, M.; Passoni, L.; Filipello, F.; Jahn, R.; Stevens, B.; Matteoli, M. Local externalization of phosphatidylserine me-diates developmental synaptic pruning by microglia. EMBO J., 2020, 39(16), e105380.
[http://dx.doi.org/10.15252/embj.2020105380] [PMID: 32657463]
[76]
Kiialainen, A.; Hovanes, K.; Paloneva, J.; Kopra, O.; Peltonen, L. Dap12 and Trem2, molecules involved in innate immunity and neuro-degeneration, are co-expressed in the CNS. Neurobiol. Dis., 2005, 18(2), 314-322.
[http://dx.doi.org/10.1016/j.nbd.2004.09.007] [PMID: 15686960]
[77]
Roumier, A.; Béchade, C.; Poncer, J.C.; Smalla, K.H.; Tomasello, E.; Vivier, E.; Gundelfinger, E.D.; Triller, A.; Bessis, A. Impaired synap-tic function in the microglial KARAP/DAP12-deficient mouse. J. Neurosci., 2004, 24(50), 11421-11428.
[http://dx.doi.org/10.1523/JNEUROSCI.2251-04.2004] [PMID: 15601948]
[78]
Wakselman, S.; Béchade, C.; Roumier, A.; Bernard, D.; Triller, A.; Bessis, A. Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. J. Neurosci., 2008, 28(32), 8138-8143.
[http://dx.doi.org/10.1523/JNEUROSCI.1006-08.2008] [PMID: 18685038]
[79]
Lehrman, E.K.; Wilton, D.K.; Litvina, E.Y.; Welsh, C.A.; Chang, S.T.; Frouin, A.; Walker, A.J.; Heller, M.D.; Umemori, H.; Chen, C.; Ste-vens, B. CD47 protects synapses from excess microglia-mediated pruning during development. Neuron, 2018, 100(1), 120-134.e6.
[http://dx.doi.org/10.1016/j.neuron.2018.09.017] [PMID: 30308165]
[80]
Varnum, M.M.; Kiyota, T.; Ingraham, K.L.; Ikezu, S.; Ikezu, T. The anti-inflammatory glycoprotein, CD200, restores neurogenesis and enhances amyloid phagocytosis in a mouse model of Alzheimer’s disease. Neurobiol. Aging, 2015, 36(11), 2995-3007.
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.07.027] [PMID: 26315370]
[81]
Lago, N.; Pannunzio, B.; Amo-Aparicio, J.; López-Vales, R.; Peluffo, H. CD200 modulates spinal cord injury neuroinflammation and outcome through CD200R1. Brain Behav. Immun., 2018, 73, 416-426.
[http://dx.doi.org/10.1016/j.bbi.2018.06.002] [PMID: 29870752]
[82]
Cohen, M.; Ben-Yehuda, H.; Porat, Z.; Raposo, C.; Gordon, S.; Schwartz, M. Newly formed endothelial cells regulate myeloid cell activity following spinal cord injury via expression of CD200 Ligand. J. Neurosci., 2017, 37(4), 972-985.
[http://dx.doi.org/10.1523/JNEUROSCI.2199-16.2016] [PMID: 28123029]
[83]
Vincenti, J.E.; Murphy, L.; Grabert, K.; McColl, B.W.; Cancellotti, E.; Freeman, T.C.; Manson, J.C.; Caughey, B. Defining the microglia response during the time course of chronic neurodegeneration. J. Virol., 2015, 90(6), 3003-3017.
[http://dx.doi.org/10.1128/JVI.02613-15] [PMID: 26719249]
[84]
Kawasaki, Y.; Zhang, L.; Cheng, J.K.; Ji, R.R. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J. Neurosci., 2008, 28(20), 5189-5194.
[http://dx.doi.org/10.1523/JNEUROSCI.3338-07.2008] [PMID: 18480275]
[85]
Lim, S.H.; Park, E.; You, B.; Jung, Y.; Park, A.R.; Park, S.G.; Lee, J.R. Neuronal synapse formation induced by microglia and interleukin 10. PLoS One, 2013, 8(11), e81218.
[http://dx.doi.org/10.1371/journal.pone.0081218] [PMID: 24278397]
[86]
Parkhurst, C.N.; Yang, G.; Ninan, I.; Savas, J.N.; Yates, J.R., III; Lafaille, J.J.; Hempstead, B.L.; Littman, D.R.; Gan, W.B. Microglia pro-mote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell, 2013, 155(7), 1596-1609.
[http://dx.doi.org/10.1016/j.cell.2013.11.030] [PMID: 24360280]
[87]
Schafer, D.P.; Jha, S.; Liu, F.; Akella, T.; McCullough, L.D.; Rasband, M.N. Disruption of the axon initial segment cytoskeleton is a new mechanism for neuronal injury. J. Neurosci., 2009, 29(42), 13242-13254.
[http://dx.doi.org/10.1523/JNEUROSCI.3376-09.2009] [PMID: 19846712]
[88]
Kumar, A.; Barrett, J.P.; Alvarez-Croda, D.M.; Stoica, B.A.; Faden, A.I.; Loane, D.J. NOX2 drives M1-like microglial/macrophage activa-tion and neurodegeneration following experimental traumatic brain injury. Brain Behav. Immun., 2016, 58, 291-309.
[http://dx.doi.org/10.1016/j.bbi.2016.07.158] [PMID: 27477920]
[89]
Paglinawan, R.; Malipiero, U.; Schlapbach, R.; Frei, K.; Reith, W.; Fontana, A. TGFbeta directs gene expression of activated microglia to an anti-inflammatory phenotype strongly focusing on chemokine genes and cell migratory genes. Glia, 2003, 44(3), 219-231.
[http://dx.doi.org/10.1002/glia.10286] [PMID: 14603463]
[90]
Mott, R.T.; Ait-Ghezala, G.; Town, T.; Mori, T.; Vendrame, M.; Zeng, J.; Ehrhart, J.; Mullan, M.; Tan, J. Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production. Glia, 2004, 46(4), 369-379.
[http://dx.doi.org/10.1002/glia.20009] [PMID: 15095367]
[91]
Brionne, T.C.; Tesseur, I.; Masliah, E.; Wyss-Coray, T. Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron, 2003, 40(6), 1133-1145.
[http://dx.doi.org/10.1016/S0896-6273(03)00766-9] [PMID: 14687548]
[92]
Hoek, R.M.; Ruuls, S.R.; Murphy, C.A.; Wright, G.J.; Goddard, R.; Zurawski, S.M.; Blom, B.; Homola, M.E.; Streit, W.J.; Brown, M.H.; Barclay, A.N.; Sedgwick, J.D. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science, 2000, 290(5497), 1768-1771.
[http://dx.doi.org/10.1126/science.290.5497.1768] [PMID: 11099416]
[93]
Walker, D.G.; Lue, L-F. Understanding the neurobiology of CD200 and the CD200 receptor: a therapeutic target for controlling inflamma-tion in human brains? Future Neurol., 2013, 8(3), 321-332.
[http://dx.doi.org/10.2217/fnl.13.14] [PMID: 24198718]
[94]
Mihrshahi, R.; Brown, M.H. Downstream of tyrosine kinase 1 and 2 play opposing roles in CD200 receptor signaling. J. Immunol., 2010, 185(12), 7216-7222.
[http://dx.doi.org/10.4049/jimmunol.1002858] [PMID: 21078907]
[95]
Mizuno, T.; Kawanokuchi, J.; Numata, K.; Suzumura, A. Production and neuroprotective functions of fractalkine in the central nervous system. Brain Res., 2003, 979(1-2), 65-70.
[http://dx.doi.org/10.1016/S0006-8993(03)02867-1] [PMID: 12850572]
[96]
Noda, M.; Doi, Y.; Liang, J.; Kawanokuchi, J.; Sonobe, Y.; Takeuchi, H.; Mizuno, T.; Suzumura, A. Fractalkine attenuates excito-neurotoxicity via microglial clearance of damaged neurons and antioxidant enzyme heme oxygenase-1 expression. J. Biol. Chem., 2011, 286(3), 2308-2319.
[http://dx.doi.org/10.1074/jbc.M110.169839] [PMID: 21071446]
[97]
Biber, K.; Neumann, H.; Inoue, K.; Boddeke, H.W.G.M. Neuronal ‘On’ and ‘Off’ signals control microglia. Trends Neurosci., 2007, 30(11), 596-602.
[http://dx.doi.org/10.1016/j.tins.2007.08.007] [PMID: 17950926]
[98]
Suzumura, A.; Sawada, M.; Yamamoto, H.; Marunouchi, T. Transforming growth factor-beta suppresses activation and proliferation of microglia in vitro. J. Immunol., 1993, 151(4), 2150-2158.
[PMID: 8345199]
[99]
Shrikant, P.; Lee, S.J.; Kalvakolanu, I.; Ransohoff, R.M.; Benveniste, E.N. Stimulus-specific inhibition of intracellular adhesion molecule-1 gene expression by TGF-beta. J. Immunol., 1996, 157(2), 892-900.
[PMID: 8752943]
[100]
Turkin, A.; Tuchina, O.; Klempin, F. Microglia function on precursor cells in the adult hippocampus and their responsiveness to serotonin signaling. Front. Cell Dev. Biol., 2021, 9(1131), 665739.
[http://dx.doi.org/10.3389/fcell.2021.665739] [PMID: 34109176]
[101]
D’Andrea, I.; Béchade, C.; Maroteaux, L. Chapter 34 - Serotonin and 5-HT2B receptors in microglia control of behavior. In: Handbook of Behavioral Neuroscience; Müller, C.P.; Cunningham, K.A., Eds.; Elsevier, 2020, 31, 589-599.
[http://dx.doi.org/10.1016/B978-0-444-64125-0.00034-7]
[102]
Glebov, K.; Löchner, M.; Jabs, R.; Lau, T.; Merkel, O.; Schloss, P.; Steinhäuser, C.; Walter, J. Serotonin stimulates secretion of exosomes from microglia cells. Glia, 2015, 63(4), 626-634.
[http://dx.doi.org/10.1002/glia.22772] [PMID: 25451814]
[103]
Pocock, J.M.; Kettenmann, H. Neurotransmitter receptors on microglia. Trends Neurosci., 2007, 30(10), 527-535.
[http://dx.doi.org/10.1016/j.tins.2007.07.007] [PMID: 17904651]
[104]
Wu, S-Y.; Pan, B-S.; Tsai, S-F.; Chiang, Y-T.; Huang, B-M.; Mo, F-E.; Kuo, Y.M. BDNF reverses aging-related microglial activation. J. Neuroinflammation, 2020, 17(1), 210.
[http://dx.doi.org/10.1186/s12974-020-01887-1] [PMID: 32664974]
[105]
Zhang, X.; Zeng, L.; Yu, T.; Xu, Y.; Pu, S.; Du, D.; Jiang, W. Positive feedback loop of autocrine BDNF from microglia causes prolonged microglia activation. Cell. Physiol. Biochem., 2014, 34(3), 715-723.
[http://dx.doi.org/10.1159/000363036] [PMID: 25171395]
[106]
Illes, P.; Rubini, P.; Ulrich, H.; Zhao, Y.; Tang, Y. Regulation of microglial functions by purinergic mechanisms in the healthy and dis-eased CNS. Cells, 2020, 9(5), 1108.
[http://dx.doi.org/10.3390/cells9051108] [PMID: 32365642]
[107]
Inoue, K. Microglial activation by purines and pyrimidines. Glia, 2002, 40(2), 156-163.
[http://dx.doi.org/10.1002/glia.10150] [PMID: 12379903]
[108]
de Jong, E.K.; Dijkstra, I.M.; Hensens, M.; Brouwer, N.; van Amerongen, M.; Liem, R.S.B.; Boddeke, H.W.; Biber, K. Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible explanation for microglia activation remote from a primary lesion. J. Neurosci., 2005, 25(33), 7548-7557.
[http://dx.doi.org/10.1523/JNEUROSCI.1019-05.2005] [PMID: 16107642]
[109]
Biber, K.; Tsuda, M.; Tozaki-Saitoh, H.; Tsukamoto, K.; Toyomitsu, E.; Masuda, T.; Boddeke, H.; Inoue, K. Neuronal CCL21 up-regulates microglia P2X4 expression and initiates neuropathic pain development. EMBO J., 2011, 30(9), 1864-1873.
[http://dx.doi.org/10.1038/emboj.2011.89] [PMID: 21441897]
[110]
Taylor, D.L.; Jones, F.; Kubota, E.S.; Pocock, J.M. Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necro-sis factor alpha-induced neurotoxicity in concert with microglial-derived Fas ligand. J. Neurosci., 2005, 25(11), 2952-2964.
[http://dx.doi.org/10.1523/JNEUROSCI.4456-04.2005] [PMID: 15772355]
[111]
Domercq, M.; Vázquez-Villoldo, N.; Matute, C. Neurotransmitter signaling in the pathophysiology of microglia. Front. Cell. Neurosci., 2013, 7(49), 49.
[http://dx.doi.org/10.3389/fncel.2013.00049] [PMID: 23626522]
[112]
Conductier, G.; Blondeau, N.; Guyon, A.; Nahon, J.L.; Rovère, C. The role of monocyte chemoattractant protein MCP1/CCL2 in neuroin-flammatory diseases. J. Neuroimmunol., 2010, 224(1-2), 93-100.
[http://dx.doi.org/10.1016/j.jneuroim.2010.05.010] [PMID: 20681057]
[113]
Tian, D.S.; Peng, J.; Murugan, M.; Feng, L.J.; Liu, J.L.; Eyo, U.B.; Zhou, L.J.; Mogilevsky, R.; Wang, W.; Wu, L.J. Chemokine CCL2-CCR2 signaling induces neuronal cell death via STAT3 activation and IL-1β production after status epilepticus. J. Neurosci., 2017, 37(33), 7878-7892.
[http://dx.doi.org/10.1523/JNEUROSCI.0315-17.2017] [PMID: 28716963]
[114]
Yao, H.; Coppola, K.; Schweig, J.E.; Crawford, F.; Mullan, M.; Paris, D. Distinct signaling pathways regulate TREM2 phagocytic and NFκB antagonistic activities. Front. Cell. Neurosci., 2019, 13(457), 457.
[http://dx.doi.org/10.3389/fncel.2019.00457]
[115]
Hsieh, C.L.; Koike, M.; Spusta, S.C.; Niemi, E.C.; Yenari, M.; Nakamura, M.C.; Seaman, W.E. A role for TREM2 ligands in the phagocy-tosis of apoptotic neuronal cells by microglia. J. Neurochem., 2009, 109(4), 1144-1156.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06042.x] [PMID: 19302484]
[116]
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]
[117]
Connolly, C.; Magnusson-Lind, A.; Lu, G.; Wagner, P.K.; Southwell, A.L.; Hayden, M.R.; Björkqvist, M.; Leavitt, B.R. Enhanced immune response to MMP3 stimulation in microglia expressing mutant huntingtin. Neuroscience, 2016, 325, 74-88.
[http://dx.doi.org/10.1016/j.neuroscience.2016.03.031] [PMID: 27033979]
[118]
Wohleb, E.S. Neuron-microglia interactions in mental health disorders: “for better, and for worse”. Front. Immunol., 2016, 7, 544.
[http://dx.doi.org/10.3389/fimmu.2016.00544] [PMID: 27965671]
[119]
Joe, E.H.; Choi, D.J.; An, J.; Eun, J.H.; Jou, I.; Park, S. Astrocytes, microglia, and Parkinson’s disease. Exp. Neurobiol., 2018, 27(2), 77-87.
[http://dx.doi.org/10.5607/en.2018.27.2.77] [PMID: 29731673]
[120]
Perea, J.R.; Llorens-Martín, M.; Ávila, J.; Bolós, M. The role of microglia in the spread of tau: relevance for tauopathies. Front. Cell. Neurosci., 2018, 12, 172.
[http://dx.doi.org/10.3389/fncel.2018.00172] [PMID: 30042659]
[121]
Ribeiro, B.M.; do Carmo, M.R.; Freire, R.S.; Rocha, N.F.; Borella, V.C.; de Menezes, A.T.; Monte, A.S.; Gomes, P.X.; de Sousa, F.C.; Vale, M.L.; de Lucena, D.F.; Gama, C.S.; Macêdo, D. Evidences for a progressive microglial activation and increase in iNOS expression in rats submitted to a neurodevelopmental model of schizophrenia: reversal by clozapine. Schizophr. Res., 2013, 151(1-3), 12-19.
[http://dx.doi.org/10.1016/j.schres.2013.10.040] [PMID: 24257517]
[122]
Ishizuka, K.; Fujita, Y.; Kawabata, T.; Kimura, H.; Iwayama, Y.; Inada, T.; Okahisa, Y.; Egawa, J.; Usami, M.; Kushima, I.; Uno, Y.; Oka-da, T.; Ikeda, M.; Aleksic, B.; Mori, D.; Someya, T.; Yoshikawa, T.; Iwata, N.; Nakamura, H.; Yamashita, T.; Ozaki, N. Rare genetic vari-ants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders. Transl. Psychiatry, 2017, 7(8), e1184.
[http://dx.doi.org/10.1038/tp.2017.173] [PMID: 28763059]
[123]
Haarman, B.C.; Riemersma-Van der Lek, R.F.; de Groot, J.C.; Ruhé, H.G.; Klein, H.C.; Zandstra, T.E.; Burger, H.; Schoevers, R.A.; de Vries, E.F.; Drexhage, H.A.; Nolen, W.A.; Doorduin, J. Neuroinflammation in bipolar disorder - A [(11)C]-(R)-PK11195 positron emis-sion tomography study. Brain Behav. Immun., 2014, 40, 219-225.
[http://dx.doi.org/10.1016/j.bbi.2014.03.016] [PMID: 24703991]
[124]
Réus, G.Z.; Fries, G.R.; Stertz, L.; Badawy, M.; Passos, I.C.; Barichello, T.; Kapczinski, F.; Quevedo, J. The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders. Neuroscience, 2015, 300, 141-154.
[http://dx.doi.org/10.1016/j.neuroscience.2015.05.018] [PMID: 25981208]
[125]
Pinto, J.V.; Passos, I.C.; Librenza-Garcia, D.; Marcon, G.; Schneider, M.A.; Conte, J.H.; da Silva, J.P.A.; Lima, L.P.; Quincozes-Santos, A.; Kauer-Sant Anna, M.; Kapczinski, F. Neuron-glia interaction as a possible pathophysiological mechanism of bipolar disorder. Curr. Neuropharmacol., 2018, 16(5), 519-532.
[http://dx.doi.org/10.2174/1570159X15666170828170921] [PMID: 28847296]
[126]
Yirmiya, R.; Rimmerman, N.; Reshef, R. Depression as a microglial disease. Trends Neurosci., 2015, 38(10), 637-658.
[http://dx.doi.org/10.1016/j.tins.2015.08.001] [PMID: 26442697]
[127]
Hellwig, S.; Brioschi, S.; Dieni, S.; Frings, L.; Masuch, A.; Blank, T.; Biber, K. Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice. Brain Behav. Immun., 2016, 55, 126-137.
[http://dx.doi.org/10.1016/j.bbi.2015.11.008] [PMID: 26576722]
[128]
Du, L.; Zhang, Y.; Chen, Y.; Zhu, J.; Yang, Y.; Zhang, H.L. Role of microglia in neurological disorders and their potentials as a therapeutic target. Mol. Neurobiol., 2017, 54(10), 7567-7584.
[http://dx.doi.org/10.1007/s12035-016-0245-0] [PMID: 27830532]
[129]
Szalay, G.; Martinecz, B.; Lénárt, N.; Környei, Z.; Orsolits, B.; Judák, L.; Császár, E.; Fekete, R.; West, B.L.; Katona, G.; Rózsa, B.; Dénes, Á. Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke. Nat. Commun., 2016, 7(1), 11499.
[http://dx.doi.org/10.1038/ncomms11499] [PMID: 27139776]
[130]
Loane, D.J.; Kumar, A. Microglia in the TBI brain: The good, the bad, and the dysregulated. Exp Neurol., 2016, 275 Pt 3(0 3), 316-327.
[http://dx.doi.org/10.1016/j.expneurol.2015.08.018] [PMID: 26342753]
[131]
Hu, X.; Li, P.; Guo, Y.; Wang, H.; Leak, R.K.; Chen, S.; Gao, Y.; Chen, J. Microglia/macrophage polarization dynamics reveal novel mech-anism of injury expansion after focal cerebral ischemia. Stroke, 2012, 43(11), 3063-3070.
[http://dx.doi.org/10.1161/STROKEAHA.112.659656] [PMID: 22933588]
[132]
Gupta, R.; Sen, N. Traumatic brain injury: a risk factor for neurodegenerative diseases. Rev. Neurosci., 2016, 27(1), 93-100.
[http://dx.doi.org/10.1515/revneuro-2015-0017] [PMID: 26352199]
[133]
Maas, A.I.R. Menon, D.K.; Adelson, P.D.; Andelic, N.; Bell, M.J.; Belli, A.; Bragge, P.; Brazinova, A.; Büki, A.; Chesnut, R.M.; Citerio, G.; Coburn, M.; Cooper, D.J.; Crowder, A.T.; Czeiter, E.; Czosnyka, M.; Diaz-Arrastia, R.; Dreier, J.P.; Duhaime, A.C.; Ercole, A.; van Es-sen, T.A.; Feigin, V.L.; Gao, G.; Giacino, J.; Gonzalez-Lara, L.E.; Gruen, R.L.; Gupta, D.; Hartings, J.A.; Hill, S.; Jiang, J.Y.; Ketharana-than, N.; Kompanje, E.J.O.; Lanyon, L.; Laureys, S.; Lecky, F.; Levin, H.; Lingsma, H.F.; Maegele, M.; Majdan, M.; Manley, G.; Marsteller, J.; Mascia, L.; McFadyen, C.; Mondello, S.; Newcombe, V.; Palotie, A.; Parizel, P.M.; Peul, W.; Piercy, J.; Polinder, S.; Puybasset, L.; Rasmussen, T.E.; Rossaint, R.; Smielewski, P.; Söderberg, J.; Stanworth, S.J.; Stein, M.B.; von Steinbüchel, N.; Stewart, W.; Steyerberg, E.W.; Stocchetti, N.; Synnot, A.; Te Ao, B.; Tenovuo, O.; Theadom, A.; Tibboel, D.; Videtta, W.; Wang, K.K.W.; Williams, W.H.; Wilson, L.; Yaffe, K.; Adams, H.; Agnoletti, V.; Allanson, J.; Amrein, K.; Andaluz, N.; Anke, A.; Antoni, A.; van As, A.B.; Audi-bert, G.; Azaševac, A.; Azouvi, P.; Azzolini, M.L.; Baciu, C.; Badenes, R.; Barlow, K.M.; Bartels, R.; Bauerfeind, U.; Beauchamp, M.; Beer, D.; Beer, R.; Belda, F.J.; Bellander, B-M.; Bellier, R.; Benali, H.; Benard, T.; Beqiri, V.; Beretta, L.; Bernard, F.; Bertolini, G.; Bilotta, F.; Blaabjerg, M.; den Boogert, H.; Boutis, K.; Bouzat, P.; Brooks, B.; Brorsson, C.; Bullinger, M.; Burns, E.; Calappi, E.; Cameron, P.; Carise, E.; Castaño-León, A.M.; Causin, F.; Chevallard, G.; Chieregato, A.; Christie, B.; Cnossen, M.; Coles, J.; Collett, J.; Della Corte, F.; Craig, W.; Csato, G.; Csomos, A.; Curry, N.; Dahyot-Fizelier, C.; Dawes, H.; DeMatteo, C.; Depreitere, B.; Dewey, D.; van Dijck, J.; Đilvesi, Đ.; Dippel, D.; Dizdarevic, K.; Donoghue, E.; Duek, O.; Dulière, G-L.; Dzeko, A.; Eapen, G.; Emery, C.A.; English, S.; Esser, P.; Ezer, E.; Fabricius, M.; Feng, J.; Fergusson, D.; Figaji, A.; Fleming, J.; Foks, K.; Francony, G.; Freedman, S.; Freo, U.; Frisvold, S.K.; Gagnon, I.; Galanaud, D.; Gantner, D.; Giraud, B.; Glocker, B.; Golubovic, J.; Gómez López, P.A.; Gordon, W.A.; Gradisek, P.; Gravel, J.; Griesdale, D.; Grossi, F.; Haagsma, J.A.; Håberg, A.K.; Haitsma, I.; Van Hecke, W.; Helbok, R.; Helseth, E.; van Heugten, C.; Hoedemaekers, C.; Höfer, S.; Horton, L.; Hui, J.; Huijben, J.A.; Hutchinson, P.J.; Jacobs, B.; van der Jagt, M.; Jankowski, S.; Janssens, K.; Jelaca, B.; Jones, K.M.; Kamnitsas, K.; Kaps, R.; Karan, M.; Katila, A.; Kaukonen, K-M.; De Keyser, V.; Kivisaari, R.; Kolias, A.G.; Kolumbán, B.; Kolundžija, K.; Kondziella, D.; Koskinen, L-O.; Kovács, N.; Kramer, A.; Kutsogiannis, D.; Kyprianou, T.; Lagares, A.; Lamontagne, F.; Latini, R.; Lauzier, F.; Lazar, I.; Ledig, C.; Lefering, R.; Legrand, V.; Levi, L.; Lightfoot, R.; Lozano, A.; MacDonald, S.; Major, S.; Mana-ra, A.; Manhes, P.; Maréchal, H.; Martino, C.; Masala, A.; Masson, S.; Mattern, J.; McFadyen, B.; McMahon, C.; Meade, M.; Melegh, B.; Menovsky, T.; Moore, L.; Morgado Correia, M.; Morganti-Kossmann, M.C.; Muehlan, H.; Mukherjee, P.; Murray, L.; van der Naalt, J.; Negru, A.; Nelson, D.; Nieboer, D.; Noirhomme, Q.; Nyirádi, J.; Oddo, M.; Okonkwo, D.O.; Oldenbeuving, A.W.; Ortolano, F.; Osmond, M.; Payen, J-F.; Perlbarg, V.; Persona, P.; Pichon, N.; Piippo-Karjalainen, A.; Pili-Floury, S.; Pirinen, M.; Ple, H.; Poca, M.A.; Posti, J.; Van Praag, D.; Ptito, A.; Radoi, A.; Ragauskas, A.; Raj, R.; Real, R.G.L.; Reed, N.; Rhodes, J.; Robertson, C.; Rocka, S.; Røe, C.; Røise, O.; Roks, G.; Rosand, J.; Rosenfeld, J.V.; Rosenlund, C.; Rosenthal, G.; Rossi, S.; Rueckert, D.; de Ruiter, G.C.W.; Sacchi, M.; Sahakian, B.J.; Sahuquillo, J.; Sakowitz, O.; Salvato, G.; Sánchez-Porras, R.; Sándor, J.; Sangha, G.; Schäfer, N.; Schmidt, S.; Schneider, K.J.; Schnyer, D.; Schöhl, H.; Schoonman, G.G.; Schou, R.F.; Sir, Ö.; Skandsen, T.; Smeets, D.; Sorinola, A.; Stamatakis, E.; Stevanovic, A.; Stevens, R.D.; Sundström, N.; Taccone, F.S.; Takala, R.; Tanskanen, P.; Taylor, M.S.; Telgmann, R.; Temkin, N.; Teodorani, G.; Thomas, M.; Tolias, C.M.; Trapani, T.; Turgeon, A.; Vajkoczy, P.; Valadka, A.B.; Valeinis, E.; Vallance, S.; Vámos, Z.; Vargiolu, A.; Vega, E.; Verheyden, J.; Vik, A.; Vilcinis, R.; Vleggeert-Lankamp, C.; Vogt, L.; Volovici, V.; Voormolen, D.C.; Vulekovic, P.; Vande Vyvere, T.; Van Waesberghe, J.; Wessels, L.; Wildschut, E.; Williams, G.; Winkler, M.K.L.; Wolf, S.; Wood, G.; Xirouchaki, N.; Younsi, A.; Zaaroor, M.; Zelinkova, V.; Zemek, R.; Zumbo, F. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol., 2017, 16(12), 987-1048.
[http://dx.doi.org/10.1016/S1474-4422(17)30371-X] [PMID: 29122524]
[134]
Simon, D.W.; McGeachy, M.J. Bayır, H.; Clark, R.S.B.; Loane, D.J.; Kochanek, P.M. The far-reaching scope of neuroinflammation after traumatic brain injury. Nat. Rev. Neurol., 2017, 13(3), 171-191.
[http://dx.doi.org/10.1038/nrneurol.2017.13] [PMID: 28186177]
[135]
Kan, E.M.; Ling, E.A.; Lu, J. Microenvironment changes in mild traumatic brain injury. Brain Res. Bull., 2012, 87(4-5), 359-372.
[http://dx.doi.org/10.1016/j.brainresbull.2012.01.007] [PMID: 22289840]
[136]
Lu, J.; Moochhala, S.; Kaur, C.; Ling, E.A. Cellular inflammatory response associated with breakdown of the blood-brain barrier after closed head injury in rats. J. Neurotrauma, 2001, 18(4), 399-408.
[http://dx.doi.org/10.1089/089771501750170976] [PMID: 11336441]
[137]
Wofford, K.L.; Loane, D.J.; Cullen, D.K. Acute drivers of neuroinflammation in traumatic brain injury. Neural Regen. Res., 2019, 14(9), 1481-1489.
[http://dx.doi.org/10.4103/1673-5374.255958] [PMID: 31089036]
[138]
DiSabato, D.J.; Quan, N.; Godbout, J.P. Neuroinflammation: the devil is in the details. J. Neurochem., 2016, 139(Suppl. 2), 136-153.
[http://dx.doi.org/10.1111/jnc.13607] [PMID: 26990767]
[139]
Lafrenaye, A.D.; Todani, M.; Walker, S.A.; Povlishock, J.T. Microglia processes associate with diffusely injured axons following mild traumatic brain injury in the micro pig. J. Neuroinflammation, 2015, 12(1), 186.
[http://dx.doi.org/10.1186/s12974-015-0405-6] [PMID: 26438203]
[140]
Alam, A.; Thelin, E.P.; Tajsic, T.; Khan, D.Z.; Khellaf, A.; Patani, R.; Helmy, A. Cellular infiltration in traumatic brain injury. J. Neuroinflammation, 2020, 17(1), 328.
[http://dx.doi.org/10.1186/s12974-020-02005-x] [PMID: 33143727]
[141]
Kaelber, S.; Pantcheva, P.; Borlongan, C.V. Drug- and cell-based therapies for targeting neuroinflammation in traumatic brain injury. Neural Regen. Res., 2016, 11(10), 1575-1576.
[http://dx.doi.org/10.4103/1673-5374.193231] [PMID: 27904484]
[142]
Witcher, K.G.; Eiferman, D.S.; Godbout, J.P. Priming the inflammatory pump of the CNS after traumatic brain injury. Trends Neurosci., 2015, 38(10), 609-620.
[http://dx.doi.org/10.1016/j.tins.2015.08.002] [PMID: 26442695]
[143]
Olmos, G.; Lladó, J. Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity. Mediators Inflamm., 2014, 2014, 861231.
[http://dx.doi.org/10.1155/2014/861231] [PMID: 24966471]
[144]
Roth, T.L.; Nayak, D.; Atanasijevic, T.; Koretsky, A.P.; Latour, L.L.; McGavern, D.B. Transcranial amelioration of inflammation and cell death after brain injury. Nature, 2014, 505(7482), 223-228.
[http://dx.doi.org/10.1038/nature12808] [PMID: 24317693]
[145]
Benusa, S.D.; Lafrenaye, A.D. Microglial process convergence on axonal segments in health and disease. Neuroimmunol. Neuroinflamm., 2020, 7(23), 23-39.
[http://dx.doi.org/10.20517/2347-8659.2019.28] [PMID: 34007863]
[146]
Eyo, U.B.; Peng, J.; Murugan, M.; Mo, M.; Lalani, A.; Xie, P.; Xu, P.; Margolis, D.J.; Wu, L-.J. Regulation of physical microglianeuron interactions by fractalkine signaling after status epilepticus. eNeuro., 2017, 3(6), ENEURO.0209-16.2016.
[http://dx.doi.org/10.1523/ENEURO.0209-16.2016] [PMID: 28101527]
[147]
Zanier, E.R.; Marchesi, F.; Ortolano, F.; Perego, C.; Arabian, M.; Zoerle, T.; Sammali, E.; Pischiutta, F.; De Simoni, M.G. Fractalkine re-ceptor deficiency is associated with early protection but late worsening of outcome following brain trauma in mice. J. Neurotrauma, 2016, 33(11), 1060-1072.
[http://dx.doi.org/10.1089/neu.2015.4041] [PMID: 26180940]
[148]
Tweedie, D.; Karnati, H.K.; Mullins, R.; Pick, C.G.; Hoffer, B.J.; Goetzl, E.J.; Kapogiannis, D.; Greig, N.H. Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury. eLife, 2020, 9, 9.
[http://dx.doi.org/10.7554/eLife.55827] [PMID: 32804078]
[149]
Wang, J.; Pan, H.; Lin, Z.; Xiong, C.; Wei, C.; Li, H.; Tong, F.; Dong, X. Neuroprotective effect of fractalkine on radiation-induced brain injury through promoting the M2 polarization of microglia. Mol. Neurobiol., 2021, 58(3), 1074-1087.
[http://dx.doi.org/10.1007/s12035-020-02138-3] [PMID: 33089423]
[150]
Mecca, C.; Giambanco, I.; Donato, R.; Arcuri, C. Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes. Int. J. Mol. Sci., 2018, 19(1), E318.
[http://dx.doi.org/10.3390/ijms19010318] [PMID: 29361745]
[151]
Yuan, P.; Condello, C.; Keene, C.D.; Wang, Y.; Bird, T.D.; Paul, S.M.; Luo, W.; Colonna, M.; Baddeley, D.; Grutzendler, J. TREM2 hap-lodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dys-trophy. Neuron, 2016, 90(4), 724-739.
[http://dx.doi.org/10.1016/j.neuron.2016.05.003] [PMID: 27196974]
[152]
Wang, Y.; Ulland, T.K.; Ulrich, J.D.; Song, W.; Tzaferis, J.A.; Hole, J.T.; Yuan, P.; Mahan, T.E.; Shi, Y.; Gilfillan, S.; Cella, M.; Grutzendler, J.; DeMattos, R.B.; Cirrito, J.R.; Holtzman, D.M.; Colonna, M. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med., 2016, 213(5), 667-675.
[http://dx.doi.org/10.1084/jem.20151948] [PMID: 27091843]
[153]
Zhao, Y.; Wu, X.; Li, X.; Jiang, L.L.; Gui, X.; Liu, Y.; Sun, Y.; Zhu, B.; Piña-Crespo, J.C.; Zhang, M.; Zhang, N.; Chen, X.; Bu, G.; An, Z.; Huang, T.Y.; Xu, H. TREM2 is a receptor for β-amyloid that mediates microglial function. Neuron, 2018, 97(5), 1023-1031.e7.
[http://dx.doi.org/10.1016/j.neuron.2018.01.031] [PMID: 29518356]
[154]
Ulrich, J.D.; Holtzman, D.M. TREM2 function in Alzheimer’s disease and neurodegeneration. ACS Chem. Neurosci., 2016, 7(4), 420-427.
[http://dx.doi.org/10.1021/acschemneuro.5b00313] [PMID: 26854967]
[155]
Jonsson, T.; Stefansson, H.; Steinberg, S.; Jonsdottir, I.; Jonsson, P.V.; Snaedal, J.; Bjornsson, S.; Huttenlocher, J.; Levey, A.I.; Lah, J.J.; Rujescu, D.; Hampel, H.; Giegling, I.; Andreassen, O.A.; Engedal, K.; Ulstein, I.; Djurovic, S.; Ibrahim-Verbaas, C.; Hofman, A.; Ikram, M.A.; van Duijn, C.M.; Thorsteinsdottir, U.; Kong, A.; Stefansson, K. Variant of TREM2 associated with the risk of Alzheimer’s disease. N. Engl. J. Med., 2013, 368(2), 107-116.
[http://dx.doi.org/10.1056/NEJMoa1211103] [PMID: 23150908]
[156]
Price, B.R.; Sudduth, T.L.; Weekman, E.M.; Johnson, S.; Hawthorne, D.; Woolums, A.; Wilcock, D.M. Therapeutic Trem2 activation ame-liorates amyloid-beta deposition and improves cognition in the 5XFAD model of amyloid deposition. J. Neuroinflammation, 2020, 17(1), 238.
[http://dx.doi.org/10.1186/s12974-020-01915-0] [PMID: 32795308]
[157]
Liu, W.; Taso, O.; Wang, R.; Bayram, S.; Graham, A.C.; Garcia-Reitboeck, P.; Mallach, A.; Andrews, W.D.; Piers, T.M.; Botia, J.A.; Po-cock, J.M.; Cummings, D.M.; Hardy, J.; Edwards, F.A.; Salih, D.A. Trem2 promotes anti-inflammatory responses in microglia and is sup-pressed under pro-inflammatory conditions. Hum. Mol. Genet., 2020, 29(19), 3224-3248.
[http://dx.doi.org/10.1093/hmg/ddaa209] [PMID: 32959884]
[158]
Ellwanger, D.C.; Wang, S.; Brioschi, S.; Shao, Z.; Green, L.; Case, R.; Yoo, D.; Weishuhn, D.; Rathanaswami, P.; Bradley, J.; Rao, S.; Cha, D.; Luan, P.; Sambashivan, S.; Gilfillan, S.; Hasson, S.A.; Foltz, I.N.; van Lookeren Campagne, M.; Colonna, M. Prior activation state shapes the microglia response to antihuman TREM2 in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2021, 118(3), e2017742118.
[http://dx.doi.org/10.1073/pnas.2017742118] [PMID: 33446504]
[159]
Jiang, S.; Bhaskar, K. Dynamics of the complement, cytokine, and chemokine systems in the regulation of synaptic function and dysfunc-tion relevant to Alzheimer’s disease. J. Alzheimers Dis., 2017, 57(4), 1123-1135.
[http://dx.doi.org/10.3233/JAD-161123] [PMID: 28372329]
[160]
Hansen, D.V.; Hanson, J.E.; Sheng, M. Microglia in Alzheimer’s disease. J. Cell Biol., 2018, 217(2), 459-472.
[http://dx.doi.org/10.1083/jcb.201709069] [PMID: 29196460]
[161]
Zhang, L.; Xu, J.; Gao, J.; Wu, Y.; Yin, M.; Zhao, W. CD200-, CX3CL1-, and TREM2-mediated neuron-microglia interactions and their involvements in Alzheimer’s disease. Rev. Neurosci., 2018, 29(8), 837-848.
[http://dx.doi.org/10.1515/revneuro-2017-0084] [PMID: 29729150]
[162]
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]
[163]
Wu, J.; Bie, B.; Yang, H.; Xu, J.J.; Brown, D.L.; Naguib, M. Suppression of central chemokine fractalkine receptor signaling alleviates amyloid-induced memory deficiency. Neurobiol. Aging, 2013, 34(12), 2843-2852.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.06.003] [PMID: 23855980]
[164]
Dworzak, J.; Renvoisé, B.; Habchi, J.; Yates, E.V.; Combadière, C.; Knowles, T.P.; Dobson, C.M.; Blackstone, C.; Paulsen, O.; Murphy, P.M. Neuronal Cx3cr1 deficiency protects against amyloid β-induced neurotoxicity. PLoS One, 2015, 10(6), e0127730.
[http://dx.doi.org/10.1371/journal.pone.0127730] [PMID: 26038823]
[165]
Kim, T-S.; Lim, H-K.; Lee, J.Y.; Kim, D-J.; Park, S.; Lee, C.; Lee, C.U. Changes in the levels of plasma soluble fractalkine in patients with mild cognitive impairment and Alzheimer’s disease. Neurosci. Lett., 2008, 436(2), 196-200.
[http://dx.doi.org/10.1016/j.neulet.2008.03.019] [PMID: 18378084]
[166]
González-Prieto, M.; Gutiérrez, I.L.; García-Bueno, B.; Caso, J.R.; Leza, J.C.; Ortega-Hernández, A.; Gómez-Garre, D.; Madrigal, J.L.M. Microglial CX3CR1 production increases in Alzheimer’s disease and is regulated by noradrenaline. Glia, 2021, 69(1), 73-90.
[http://dx.doi.org/10.1002/glia.23885] [PMID: 32662924]
[167]
Nash, K.R.; Moran, P.; Finneran, D.J.; Hudson, C.; Robinson, J.; Morgan, D.; Bickford, P.C. Fractalkine over expression suppresses α-synuclein-mediated neurodegeneration. Mol. Ther., 2015, 23(1), 17-23.
[http://dx.doi.org/10.1038/mt.2014.175] [PMID: 25195598]
[168]
Morganti, J.M.; Nash, K.R.; Grimmig, B.A.; Ranjit, S.; Small, B.; Bickford, P.C.; Gemma, C. The soluble isoform of CX3CL1 is necessary for neuroprotection in a mouse model of Parkinson’s disease. J. Neurosci., 2012, 32(42), 14592-14601.
[http://dx.doi.org/10.1523/JNEUROSCI.0539-12.2012] [PMID: 23077045]
[169]
Pabon, M.M.; Bachstetter, A.D.; Hudson, C.E.; Gemma, C.; Bickford, P.C. CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson’s disease. J. Neuroinflammation, 2011, 8(1), 9.
[http://dx.doi.org/10.1186/1742-2094-8-9] [PMID: 21266082]
[170]
CDC. Stroke 2020 (cited 2021 7th february, 2021). Available from: https://www.cdc.gov/stroke/about.htm
[171]
Kowalski, R.G.; Haarbauer-Krupa, J.K.; Bell, J.M.; Corrigan, J.D.; Hammond, F.M.; Torbey, M.T.; Hofmann, M.C.; Dams-O’Connor, K.; Miller, A.C.; Whiteneck, G.G. Acute ischemic stroke after moderate to severe traumatic brain injury: incidence and impact on outcome. Stroke, 2017, 48(7), 1802-1809.
[http://dx.doi.org/10.1161/STROKEAHA.117.017327] [PMID: 28611087]
[172]
Jayaraj, R.L.; Azimullah, S.; Beiram, R.; Jalal, F.Y.; Rosenberg, G.A. Neuroinflammation: friend and foe for ischemic stroke. J. Neuroinflammation, 2019, 16(1), 142.
[http://dx.doi.org/10.1186/s12974-019-1516-2] [PMID: 31291966]
[173]
Chen, Y.; Won, S.J.; Xu, Y.; Swanson, R.A. Targeting microglial activation in stroke therapy: pharmacological tools and gender effects. Curr. Med. Chem., 2014, 21(19), 2146-2155.
[http://dx.doi.org/10.2174/0929867321666131228203906] [PMID: 24372213]
[174]
Kawabori, M.; Kacimi, R.; Kauppinen, T.; Calosing, C.; Kim, J.Y.; Hsieh, C.L.; Nakamura, M.C.; Yenari, M.A. Triggering receptor ex-pressed on myeloid cells 2 (TREM2) deficiency attenuates phagocytic activities of microglia and exacerbates ischemic damage in experi-mental stroke. J. Neurosci., 2015, 35(8), 3384-3396.
[http://dx.doi.org/10.1523/JNEUROSCI.2620-14.2015] [PMID: 25716838]
[175]
Gülke, E.; Gelderblom, M.; Magnus, T. Danger signals in stroke and their role on microglia activation after ischemia. Ther. Adv. Neurol. Disord., 2018, 11, 1756286418774254.
[http://dx.doi.org/10.1177/1756286418774254] [PMID: 29854002]
[176]
Ponomarev, E.D.; Shriver, L.P.; Maresz, K.; Dittel, B.N. Microglial cell activation and proliferation precedes the onset of CNS autoim-munity. J. Neurosci. Res., 2005, 81(3), 374-389.
[http://dx.doi.org/10.1002/jnr.20488] [PMID: 15959904]
[177]
Prinz, M.; Priller, J.; Sisodia, S.S.; Ransohoff, R.M. Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat. Neurosci., 2011, 14(10), 1227-1235.
[http://dx.doi.org/10.1038/nn.2923] [PMID: 21952260]
[178]
Heindl, S.; Gesierich, B.; Benakis, C.; Llovera, G.; Duering, M.; Liesz, A. Automated morphological analysis of microglia after stroke. Front. Cell. Neurosci., 2018, 12, 106.
[http://dx.doi.org/10.3389/fncel.2018.00106] [PMID: 29725290]
[179]
Ransohoff, R.M.; Perry, V.H. Microglial physiology: unique stimuli, specialized responses. Annu. Rev. Immunol., 2009, 27(1), 119-145.
[http://dx.doi.org/10.1146/annurev.immunol.021908.132528] [PMID: 19302036]
[180]
Ju, F.; Ran, Y.; Zhu, L.; Cheng, X.; Gao, H.; Xi, X.; Yang, Z.; Zhang, S. Increased BBB permeability enhances activation of microglia and exacerbates loss of dendritic spines after transient global cerebral ischemia. Front. Cell. Neurosci., 2018, 12, 236.
[http://dx.doi.org/10.3389/fncel.2018.00236] [PMID: 30123113]
[181]
Masuda, T.; Croom, D.; Hida, H.; Kirov, S.A. Capillary blood flow around microglial somata determines dynamics of microglial processes in ischemic conditions. Glia, 2011, 59(11), 1744-1753.
[http://dx.doi.org/10.1002/glia.21220] [PMID: 21800362]
[182]
Li, T.; Pang, S.; Yu, Y.; Wu, X.; Guo, J.; Zhang, S. Proliferation of parenchymal microglia is the main source of microgliosis after is-chaemic stroke. Brain, 2013, 136(Pt 12), 3578-3588.
[http://dx.doi.org/10.1093/brain/awt287] [PMID: 24154617]
[183]
Denes, A.; McColl, B.W.; Leow-Dyke, S.F.; Chapman, K.Z.; Humphreys, N.E.; Grencis, R.K.; Allan, S.M.; Rothwell, N.J. Experimental stroke-induced changes in the bone marrow reveal complex regulation of leukocyte responses. J. Cereb. Blood Flow Metab., 2011, 31(4), 1036-1050.
[http://dx.doi.org/10.1038/jcbfm.2010.198] [PMID: 21045863]
[184]
Franco, E.C.; Cardoso, M.M.; Gouvêia, A.; Pereira, A.; Gomes-Leal, W. Modulation of microglial activation enhances neuroprotection and functional recovery derived from bone marrow mononuclear cell transplantation after cortical ischemia. Neurosci. Res., 2012, 73(2), 122-132.
[http://dx.doi.org/10.1016/j.neures.2012.03.006] [PMID: 22465414]
[185]
Neher, J.J.; Emmrich, J.V.; Fricker, M.; Mander, P.K.; Théry, C.; Brown, G.C. Phagocytosis executes delayed neuronal death after focal brain ischemia. Proc. Natl. Acad. Sci. USA, 2013, 110(43), E4098-E4107.
[http://dx.doi.org/10.1073/pnas.1308679110] [PMID: 24101459]
[186]
Ma, Y.; Wang, J.; Wang, Y.; Yang, G.Y. The biphasic function of microglia in ischemic stroke. Prog. Neurobiol., 2017, 157, 247-272.
[http://dx.doi.org/10.1016/j.pneurobio.2016.01.005] [PMID: 26851161]
[187]
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]
[188]
Hanisch, U.K.; Kettenmann, H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci., 2007, 10(11), 1387-1394.
[http://dx.doi.org/10.1038/nn1997] [PMID: 17965659]
[189]
Neumann, J.; Gunzer, M.; Gutzeit, H.O.; Ullrich, O.; Reymann, K.G.; Dinkel, K. Microglia provide neuroprotection after ischemia. FASEB J., 2006, 20(6), 714-716.
[http://dx.doi.org/10.1096/fj.05-4882fje] [PMID: 16473887]
[190]
Neumann, J.; Sauerzweig, S.; Rönicke, R.; Gunzer, F.; Dinkel, K.; Ullrich, O.; Gunzer, M.; Reymann, K.G. Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege. J. Neurosci., 2008, 28(23), 5965-5975.
[http://dx.doi.org/10.1523/JNEUROSCI.0060-08.2008] [PMID: 18524901]
[191]
Neumann, H. Control of glial immune function by neurons. Glia, 2001, 36(2), 191-199.
[http://dx.doi.org/10.1002/glia.1108] [PMID: 11596127]
[192]
Yang, Y.; Zhang, X.J.; Zhang, C.; Chen, R.; Li, L.; He, J.; Xie, Y.; Chen, Y. Loss of neuronal CD200 contributed to microglial activation after acute cerebral ischemia in mice. Neurosci. Lett., 2018, 678, 48-54.
[http://dx.doi.org/10.1016/j.neulet.2018.05.004] [PMID: 29729356]
[193]
Dénes, A.; Ferenczi, S.; Halász, J.; Környei, Z.; Kovács, K.J. Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse. J. Cereb. Blood Flow Metab., 2008, 28(10), 1707-1721.
[http://dx.doi.org/10.1038/jcbfm.2008.64] [PMID: 18575457]
[194]
Deng, Y.; Tan, R.; Li, F.; Liu, Y.; Shi, J.; Gong, Q. Isorhynchophylline ameliorates cerebral ischemia/reperfusion injury by inhibiting CX3CR1-mediated microglial activation and neuroinflammation. Front. Pharmacol., 2021, 12, 574793.
[http://dx.doi.org/10.3389/fphar.2021.574793] [PMID: 33643044]
[195]
Cipriani, R.; Villa, P.; Chece, G.; Lauro, C.; Paladini, A.; Micotti, E.; Perego, C.; De Simoni, M.G.; Fredholm, B.B.; Eusebi, F.; Limatola, C. CX3CL1 is neuroprotective in permanent focal cerebral ischemia in rodents. J. Neurosci., 2011, 31(45), 16327-16335.
[http://dx.doi.org/10.1523/JNEUROSCI.3611-11.2011] [PMID: 22072684]
[196]
Donohue, M.M.; Cain, K.; Zierath, D.; Shibata, D.; Tanzi, P.M.; Becker, K.J. Higher plasma fractalkine is associated with better 6-month outcome from ischemic stroke. Stroke, 2012, 43(9), 2300-2306.
[http://dx.doi.org/10.1161/STROKEAHA.112.657411] [PMID: 22798324]
[197]
Chen, X.; Jiang, M.; Li, H.; Wang, Y.; Shen, H.; Li, X.; Zhang, Y.; Wu, J.; Yu, Z.; Chen, G. CX3CL1/CX3CR1 axis attenuates early brain injury via promoting the delivery of exosomal microRNA-124 from neuron to microglia after subarachnoid hemorrhage. J. Neuroinflammation, 2020, 17(1), 209.
[http://dx.doi.org/10.1186/s12974-020-01882-6] [PMID: 32664984]
[198]
Denieffe, S.; Kelly, R.J.; McDonald, C.; Lyons, A.; Lynch, M.A. Classical activation of microglia in CD200-deficient mice is a conse-quence of blood brain barrier permeability and infiltration of peripheral cells. Brain Behav. Immun., 2013, 34, 86-97.
[http://dx.doi.org/10.1016/j.bbi.2013.07.174] [PMID: 23916893]
[199]
Hayakawa, K.; Pham, L-D.D.; Seo, J.H.; Miyamoto, N.; Maki, T.; Terasaki, Y. Sakadžić S.; Boas, D.; van Leyen, K.; Waeber, C.; Kim, K.W.; Arai, K.; Lo, E.H. CD200 restrains macrophage attack on oligodendrocyte precursors via toll-like receptor 4 downregulation. J. Cereb. Blood Flow Metab., 2016, 36(4), 781-793.
[http://dx.doi.org/10.1177/0271678X15606148] [PMID: 26661156]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy