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01-05-2015 | Original Article

Patrolling monocytes play a critical role in CX3CR1-mediated neuroprotection during excitotoxicity

Authors: Marc-André Bellavance, David Gosselin, V. Wee Yong, Peter K. Stys, Serge Rivest

Published in: Brain Structure and Function | Issue 3/2015

Abstract

Excitotoxicity underlies neuronal death in many neuropathological disorders, such as Alzheimer’s disease and multiple sclerosis. In murine models of these diseases, disruption of CX3CR1 signaling has thus far generated data either in favor or against a neuroprotective role of this crucial regulator of microglia and monocyte functions. In this study, we investigated the recruitment of circulating PU.1-expressing cells following sterile excitotoxicity and delineated the CX3CR1-dependent neuroprotective functions of circulating monocytes versus that of microglia in this context. WT, Cx3cr1-deficient and chimeric mice were subjected to a sterile excitotoxic insult via an intrastriatal injection of kainic acid (KA), a conformational analog of glutamate. Following KA administration, circulating monocytes physiologically engrafted the brain and selectively accumulated in the vicinity of excitotoxic lesions where they gave rise to activated macrophages depicting strong Iba1 and CD68 immunoreactivity 7 days post-injury. Monocyte-derived macrophages completely vanished upon recovery and did thus not permanently seed the brain. Furthermore, Cx3cr1 deletion significantly exacerbated neuronal death, behavioral deficits and activation of microglia cells following sterile excitotoxicity. Cx3cr1 disruption also markedly altered the blood levels of patrolling monocytes 24 h after KA administration. The specific elimination of patrolling monocytes using Nr4a1 ^−/− chimeric mice conditioned with chemotherapy provided direct evidence that these circulating monocytes are essential for neuroprotection. Taken together, these data support a beneficial role of CX3CR1 signaling during excitotoxicity and highlight a novel and pivotal role of patrolling monocytes in neuroprotection. These findings open new research and therapeutic avenues for neuropathological disorders implicating excitotoxicity.

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Ajami B, Bennett JL, Krieger C et al (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10:1538–1543. doi:10.1038/nn2014 CrossRefPubMed

Ajami B, Bennett JL, Krieger C et al (2011) Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat Neurosci. doi:10.1038/nn.2887 PubMed

Auffray C, Fogg D, Garfa M et al (2007) Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317:666–670. doi:10.1126/science.1142883 CrossRefPubMed

Babcock AA, Kuziel WA, Rivest S, Owens T (2003) Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J Neurosci 23:7922–7930PubMed

Ben Ari Y (2010) Kainate and temporal lobe epilepsies: three decades of progress. Epilepsia 51:40CrossRef

Biber K, Zuurman MW, Dijkstra IM, Boddeke HWGM (2002) Chemokines in the brain: neuroimmunology and beyond. Curr Opin Pharmacol 2:63–68. doi:10.1016/S1471-4892(01)00122-9 CrossRefPubMed

Block ML, Zecca L, Hong J-S (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57–69. doi:10.1038/nrn2038 CrossRefPubMed

Boissonneault V, Filali M, Lessard M et al (2009) Powerful beneficial effects of macrophage colony-stimulating factor on beta-amyloid deposition and cognitive impairment in Alzheimer’s disease. Brain 132:1078–1092. doi:10.1093/brain/awn331 CrossRefPubMed

Butovsky O, Jedrychowski MP, Moore CS et al (2014) Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 17:131–143. doi:10.1038/nn.3599 CrossRefPubMedCentralPubMed

Capotondo A, Milazzo R, Politi LS et al (2012) Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation. Proc Natl Acad Sci USA. doi:10.1073/pnas.1205858109 PubMedCentralPubMed

Cardona AE, Pioro EP, Sasse ME et al (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9:917–924. doi:10.1038/nn1715 CrossRefPubMed

Carlin LM, Stamatiades EG, Auffray C et al (2013) Nr4a1-dependent Ly6Clow monocytes monitor endothelial cells and orchestrate their disposal. Cell 153:362–375. doi:10.1016/j.cell.2013.03.010 CrossRefPubMedCentralPubMed

Carotta S, Dakic A, D’Amico A et al (2010) The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner. Immunity 32:628–641. doi:10.1016/j.immuni.2010.05.005 CrossRefPubMed

Cartier N, Hacein-Bey-Abina S, Bartholomae CC et al (2009) Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326:818–823. doi:10.1126/science.1171242 CrossRefPubMed

Chapman GA, Moores K, Harrison D et al (2000) Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci 20:RC87PubMed

Dakic A, Metcalf D, Di Rago L et al (2005) PU.1 regulates the commitment of adult hematopoietic progenitors and restricts granulopoiesis. J Exp Med 201:1487–1502. doi:10.1084/jem.20050075 CrossRefPubMedCentralPubMed

Davalos D, Grutzendler J, Yang G et al (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758. doi:10.1038/nn1472 CrossRefPubMed

de Haas AH, Boddeke HWGM, Brouwer N, Biber K (2007) Optimized isolation enables ex vivo analysis of microglia from various central nervous system regions. Glia 55:1374–1384. doi:10.1002/glia.20554 CrossRefPubMed

Derecki NC, Cronk JC, Lu Z et al (2012) Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484:105–109. doi:10.1038/nature10907 CrossRefPubMedCentralPubMed

Donnelly DJ, Longbrake EE, Shawler TM et al (2011) Deficient CX3CR1 signaling promotes recovery after mouse spinal cord injury by limiting the recruitment and activation of Ly6Clo/iNOS+ macrophages. J Neurosci 31:9910–9922. doi:10.1523/JNEUROSCI.2114-11.2011 CrossRefPubMedCentralPubMed

Drevets DA, Dillon MJ, Schawang JE et al (2010) IFN-gamma triggers CCR2-independent monocyte entry into the brain during systemic infection by virulent Listeria monocytogenes. Brain Behav Immun 24:919–929. doi:10.1016/j.bbi.2010.02.011 CrossRefPubMed

Ethier I, Beaudry G, St-Hilaire M et al (2004) The transcription factor NGFI-B (Nur77) and retinoids play a critical role in acute neuroleptic-induced extrapyramidal effect and striatal neuropeptide gene expression. Neuropsychopharmacology 29:335–346. doi:10.1038/sj.npp.1300318 CrossRefPubMed

Flügel A, Hager G, Horvat A et al (2001) Neuronal MCP-1 expression in response to remote nerve injury. J Cereb Blood Flow Metab 21:69–76. doi:10.1097/00004647-200101000-00009 CrossRefPubMed

Francis JS, Dragunow M, During MJ (2004) Over expression of ATF-3 protects rat hippocampal neurons from in vivo injection of kainic acid. Brain Res Mol Brain Res 124:199–203. doi:10.1016/j.molbrainres.2003.10.027 CrossRefPubMed

Gamo K, Kiryu-Seo S, Konishi H et al (2008) G-protein-coupled receptor screen reveals a role for chemokine receptor CCR5 in suppressing microglial neurotoxicity. J Neurosci 28:11980–11988. doi:10.1523/JNEUROSCI.2920-08.2008 CrossRefPubMed

Garcia JH, Wagner S, Liu KF, Hu XJ (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats: statistical validation. Stroke 26:627–635. doi:10.1161/01.STR.26.4.627 CrossRefPubMed

Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82. doi:10.1016/S1074-7613(03)00174-2 CrossRefPubMed

Ginhoux F, Greter M, Leboeuf M et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845. doi:10.1126/science.1194637 CrossRefPubMedCentralPubMed

Gosselin D, Bellavance M-A, Rivest S (2013) IL-1RAcPb signaling regulates adaptive mechanisms in neurons that promote their long-term survival following excitotoxic insults. Front Cell Neurosci 7:9. doi:10.3389/fncel.2013.00009 PubMedCentralPubMed

Hanisch U-K, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394. doi:10.1038/nn1997 CrossRefPubMed

Hanna RN, Carlin LM, Hubbeling HG et al (2011) The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C-monocytes. Nat Immunol 12:778–785. doi:10.1038/ni.2063 CrossRefPubMedCentralPubMed

Hanna RN, Shaked I, Hubbeling HG et al (2012) NR4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis. Circ Res 110:416–427. doi:10.1161/CIRCRESAHA.111.253377 CrossRefPubMedCentralPubMed

Harrison JK, Jiang Y, Chen S et al (1998) Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci USA 95:10896–10901. doi:10.1073/pnas.95.18.10896 CrossRefPubMedCentralPubMed

Hasegawa-Ishii S, Takei S, Inaba M et al (2011) Defects in cytokine-mediated neuroprotective glial responses to excitotoxic hippocampal injury in senescence-accelerated mouse. Brain Behav Immun 25:83–100. doi:10.1016/j.bbi.2010.08.006 CrossRefPubMed

Haynes SE, Hollopeter G, Yang G et al (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9:1512–1519. doi:10.1038/nn1805 CrossRefPubMed

Heinz S, Benner C, Spann N et al (2010) Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38:576–589. doi:10.1016/j.molcel.2010.05.004 CrossRefPubMedCentralPubMed

Hellwig S, Heinrich A, Biber K (2013) The brain’s best friend: microglial neurotoxicity revisited. Front Cell Neurosci 7:71. doi:10.3389/fncel.2013.00071 CrossRefPubMedCentralPubMed

Hoshiko M, Arnoux I, Avignone E et al (2012) Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex. J Neurosci 32:15106–15111. doi:10.1523/JNEUROSCI.1167-12.2012 CrossRefPubMed

Hosmane S, Tegenge MA, Rajbhandari L et al (2012) Toll/interleukin-1 receptor domain-containing adapter inducing interferon-β mediates microglial phagocytosis of degenerating axons. J Neurosci 32:7745–7757. doi:10.1523/JNEUROSCI.0203-12.2012 CrossRefPubMedCentralPubMed

Hunsberger JG, Bennett AH, Selvanayagam E et al (2005) Gene profiling the response to kainic acid induced seizures. Brain Res Mol Brain Res 141:95–112. doi:10.1016/j.molbrainres.2005.08.005 CrossRefPubMed

Imai T, Hieshima K, Haskell C et al (1997) Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91:521–530. doi:10.1016/S0092-8674(00)80438-9 CrossRefPubMed

Jacquelin S, Licata F, Dorgham K et al (2013) CX3CR1 reduces Ly6Chigh-monocyte motility within and release from the bone marrow after chemotherapy in mice. Blood 122:674–683. doi:10.1182/blood-2013-01-480749 CrossRefPubMed

Jin F, Li Y, Ren B, Natarajan R (2011) PU.1 and C/EBP(alpha) synergistically program distinct response to NF-kappaB activation through establishing monocyte specific enhancers. Proc Natl Acad Sci USA 108:5290–5295. doi:10.1073/pnas.1017214108 CrossRefPubMedCentralPubMed

Kierdorf K, Prinz M (2013) Factors regulating microglia activation. Front Cell Neurosci 7:44. doi:10.3389/fncel.2013.00044 CrossRefPubMedCentralPubMed

Kierdorf K, Erny D, Goldmann T et al (2013) Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci 16:273–280. doi:10.1038/nn.3318 CrossRefPubMed

Kueh HY, Champhekar A, Nutt SL et al (2013) Positive feedback between PU.1 and the cell cycle controls myeloid differentiation. Science 341:670–673. doi:10.1126/science.1240831 CrossRefPubMedCentralPubMed

Laflamme N, Rivest S (2001) Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gram-negative bacterial cell wall components. FASEB J 15:155–163. doi:10.1096/fj.00-0339com CrossRefPubMed

Lampron A, Lessard M, Rivest S (2012) Effects of myeloablation, peripheral chimerism, and whole-body irradiation on the entry of bone marrow-derived cells into the brain. Cell Transplant 21:1149–1159. doi:10.3727/096368911X593154 CrossRefPubMed

Landsman L, Bar-On L, Zernecke A et al (2009) CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 113:963–972. doi:10.1182/blood-2008-07-170787 CrossRefPubMed

Laurén HB, Lopez-Picon FR, Brandt AM et al (2010) Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats. PLoS One 5:e10733. doi:10.1371/journal.pone.0010733 CrossRefPubMedCentralPubMed

Lee S, Kim J-H, Kim J-H et al (2011) Lipocalin-2 Is a chemokine inducer in the central nervous system: role of chemokine ligand 10 (CXCL10) in lipocalin-2-induced cell migration. J Biol Chem 286:43855–43870. doi:10.1074/jbc.M111.299248 CrossRefPubMedCentralPubMed

Limatola C, Lauro C, Catalano M et al (2005) Chemokine CX3CL1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity. J Neuroimmunol 166:19–28. doi:10.1016/j.jneuroim.2005.03.023 CrossRefPubMed

Liu L, Hamre KM, Goldowitz D (2012) Kainic acid-induced neuronal degeneration in hippocampal pyramidal neurons is driven by both intrinsic and extrinsic factors: analysis of FVB/N{leftrightarrow}C57BL/6 Chimeras. J Neurosci 32:12093–12101. doi:10.1523/JNEUROSCI.6478-11.2012 CrossRefPubMed

London A, Cohen M, Schwartz M (2013) Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair. Front Cell Neurosci 7:34. doi:10.3389/fncel.2013.00034 CrossRefPubMedCentralPubMed

Mak KS, Funnell APW, Pearson RCM, Crossley M (2011) PU.1 and haematopoietic cell fate: dosage matters. Int J Cell Biol 2011:808524. doi:10.1155/2011/808524 CrossRefPubMedCentralPubMed

Michaud J-P, Bellavance M-A, Préfontaine P, Rivest S (2013) Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta. Cell Rep 5:646–653. doi:10.1016/j.celrep.2013.10.010 CrossRefPubMed

Mildner A, Schmidt H, Nitsche M et al (2007) Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat Neurosci 10:1544–1553. doi:10.1038/nn2015 CrossRefPubMed

Mildner A, Schlevogt B, Kierdorf K et al (2011) Distinct and non-redundant roles of microglia and myeloid subsets in mouse models of Alzheimer’s disease. J Neurosci 31:11159–11171. doi:10.1523/JNEUROSCI.6209-10.2011 CrossRefPubMed

Motti D, Le Duigou C, Eugène E et al (2010) Gene expression analysis of the emergence of epileptiform activity after focal injection of kainic acid into mouse hippocampus. Eur J Neurosci 32:1364–1379. doi:10.1111/j.1460-9568.2010.07403.x CrossRefPubMed

Nahrendorf M, Swirski FK, Aikawa E et al (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047. doi:10.1084/jem.20070885 CrossRefPubMedCentralPubMed

Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318. doi:10.1126/science.1110647 CrossRefPubMed

Noda M, Doi Y, Liang J et al (2011) Fractalkine attenuates excito-neurotoxicity via microglial clearance of damaged neurons and antioxidant enzyme heme oxygenase-1 expression. J Biol Chem 286:2308–2319. doi:10.1074/jbc.M110.169839 CrossRefPubMedCentralPubMed

Nutt SL, Metcalf D, D’Amico A et al (2005) Dynamic regulation of PU.1 expression in multipotent hematopoietic progenitors. J Exp Med 201:221–231. doi:10.1084/jem.20041535 CrossRefPubMedCentralPubMed

Paolicelli RC, Bolasco G, Pagani F et al (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333:1456–1458. doi:10.1126/science.1202529 CrossRefPubMed

Pimentel-Coelho PM, Michaud J-P, Rivest S (2013) Evidence for a gender-specific protective role of innate immune receptors in a model of perinatal brain injury. J Neurosci 33:11556–11572. doi:10.1523/JNEUROSCI.0535-13.2013 CrossRefPubMed

Ponomarev ED, Veremeyko T, Barteneva N et al (2011) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway. Nat Med 17:64–70. doi:10.1038/nm.2266 CrossRefPubMedCentralPubMed

Prinz M, Priller J (2010) Tickets to the brain: role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. J Neuroimmunol 224:80–84. doi:10.1016/j.jneuroim.2010.05.015 CrossRefPubMed

Prinz M, Priller J, Sisodia SS, Ransohoff RM (2011) Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci 14:1227–1235. doi:10.1038/nn.2923 CrossRefPubMed

Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281–294. doi:10.1016/0013-4694(72)90177-0 CrossRefPubMed

Ransohoff RM, Liu L, Cardona AE (2007) Chemokines and chemokine receptors: multipurpose players in neuroinflammation. Int Rev Neurobiol 85(82):187–204. doi:10.1016/S0074-7742(07)82010-1 CrossRef

Rivest S (2009) Regulation of innate immune responses in the brain. Nat Rev Immunol 9:429–439. doi:10.1038/nri2565 CrossRefPubMed

Rogers JT, Morganti JM, Bachstetter AD et al (2011) CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. J Neurosci 31:16241–16250. doi:10.1523/JNEUROSCI.3667-11.2011 CrossRefPubMed

Schmued LC, Hopkins KJ (2000) Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874:123–130. doi:10.1016/S0006-8993(00)02513-0 CrossRefPubMed

Schulz C, Gomez Perdiguero E, Chorro L et al (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:86–90. doi:10.1126/science.1219179 CrossRefPubMed

Shechter R, Miller O, Yovel G et al (2013) Recruitment of beneficial m2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity 38:555–569. doi:10.1016/j.immuni.2013.02.012 CrossRefPubMedCentralPubMed

Sieger D, Moritz C, Ziegenhals T et al (2012) Long-range Ca2+ waves transmit brain-damage signals to microglia. Dev Cell 22:1138–1148. doi:10.1016/j.devcel.2012.04.012 CrossRefPubMed

Simard AR, Rivest S (2004) Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia. FASEB J 18:998–1000. doi:10.1096/fj.04-1517fje PubMed

Simard AR, Soulet D, Gowing G et al (2006) Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49:489–502. doi:10.1016/j.neuron.2006.01.022 CrossRefPubMed

Soulet D, Rivest S (2008) Bone-marrow-derived microglia: myth or reality? Curr Opin Pharmacol 8:508–518. doi:10.1016/j.coph.2008.04.002 CrossRefPubMed

Tremblay M-È, Lowery RL, Majewska AK (2010) Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8:e1000527. doi:10.1371/journal.pbio.1000527 CrossRefPubMedCentralPubMed

Ueno M, Fujita Y, Tanaka T et al (2013) Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci 16:543–551. doi:10.1038/nn.3358 CrossRefPubMed

Vincent P, Mulle C (2009) Kainate receptors in epilepsy and excitotoxicity. Neuroscience 158:309–323. doi:10.1016/j.neuroscience.2008.02.066 CrossRefPubMed

Wake H, Moorhouse AJ, Jinno S et al (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29:3974–3980. doi:10.1523/JNEUROSCI.4363-08.2009 CrossRefPubMed

Wake H, Moorhouse AJ, Miyamoto A, Nabekura J (2013) Microglia: actively surveying and shaping neuronal circuit structure and function. Trends Neurosci 36:209–217. doi:10.1016/j.tins.2012.11.007 CrossRefPubMed

Wang L, Liu Y-H, Huang Y-G, Chen L-W (2008) Time-course of neuronal death in the mouse pilocarpine model of chronic epilepsy using Fluoro-Jade C staining. Brain Res 1241:157–167. doi:10.1016/j.brainres.2008.07.097 CrossRefPubMed

Wilkinson FL, Sergijenko A, Langford-Smith KJ et al (2013) Busulfan conditioning enhances engraftment of hematopoietic donor-derived cells in the brain compared with irradiation. Mol Ther 21:868–876. doi:10.1038/mt.2013.29 CrossRefPubMedCentralPubMed

Wilson EH, Weninger W, Hunter CA (2010) Trafficking of immune cells in the central nervous system. J Clin Invest 120:1368–1379. doi:10.1172/JCI41911 CrossRefPubMedCentralPubMed

Yong VW, Rivest S (2009) Taking advantage of the systemic immune system to cure brain diseases. Neuron 64:55–60. doi:10.1016/j.neuron.2009.09.035 CrossRefPubMed

Zhang XM, Zhu J (2011) Kainic acid-induced neurotoxicity: targeting glial responses and glia-derived cytokines. Curr Neuropharmacol 9:388. doi:10.2174/157015911795596540 CrossRefPubMedCentralPubMed

Title: Patrolling monocytes play a critical role in CX3CR1-mediated neuroprotection during excitotoxicity
Authors: Marc-André Bellavance
David Gosselin
V. Wee Yong
Peter K. Stys
Serge Rivest
Publication date: 01-05-2015
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 3/2015
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-014-0759-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Patrolling monocytes play a critical role in CX3CR1-mediated neuroprotection during excitotoxicity

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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