{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:53:24Z","timestamp":1791201204513,"version":"4.2.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,1,16]],"date-time":"2012-01-16T00:00:00Z","timestamp":1326672000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"},{"start":{"date-parts":[[2012,1,16]],"date-time":"2012-01-16T00:00:00Z","timestamp":1326672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, presents typically as ascending paralysis. However, in mice in which interferon-gamma (IFN\u03b3) signaling is disrupted by genetic deletion, limb paralysis is accompanied by atypical deficits, including head tilt, postural imbalance, and circling, consistent with cerebellar\/vestibular dysfunction. This was previously attributed to intense cerebellar and brainstem infiltration by peripheral immune cells and formation of neutrophil-rich foci within the CNS. However, the exact mechanism by which IFN\u03b3 signaling prohibits the development of vestibular deficits, and whether the distribution and composition of inflammatory foci within the CNS affects the course of atypical EAE remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We induced EAE in IFN\u03b3-\/- mice and bone marrow chimeric mice in which IFN\u03b3R is not expressed in the CNS but is intact in the periphery (IFN\u03b3R<jats:sup>CNS<\/jats:sup>KO) and vice versa (IFN\u03b3R<jats:sup>peri<\/jats:sup>KO). Blood-brain barrier permeability was determined by Evans blue intravenous administration at disease onset. Populations of immune cell subsets in the periphery and the CNS were quantified by flow cytometry. CNS tissues isolated at various time points after EAE induction, were analyzed by immunohistochemistry for composition of inflammatory foci and patterns of axonal degeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Incidence and severity of atypical EAE were more pronounced in IFN\u03b3R<jats:sup>CNS<\/jats:sup>KO as compared to IFN\u03b3R<jats:sup>peri<\/jats:sup>KO mice. Contrary to what we anticipated, cerebella\/brainstems of IFN\u03b3R<jats:sup>CNS<\/jats:sup>KO mice were only minimally infiltrated, while the same areas of IFN\u03b3R<jats:sup>peri<\/jats:sup>KO mice were extensively populated by peripheral immune cells. Furthermore, the CNS of IFN\u03b3R<jats:sup>peri<\/jats:sup>KO mice was characterized by persistent neutrophil-rich foci as compared to IFN\u03b3R<jats:sup>CNS<\/jats:sup>KO. Immunohistochemical analysis of the CNS of IFN\u03b3-\/- and IFN\u03b3R chimeric mice revealed that IFN\u03b3 protective actions are exerted through microglial STAT1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alterations in distribution and composition of CNS inflammatory foci are not sufficient for the onset of atypical EAE. IFN\u03b3 dictates the course of neuroinflammatory disorders mainly through actions exerted within the CNS. This study provides strong evidence that link microglial STAT1 inactivation to vestibular dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1742-2094-9-7","type":"journal-article","created":{"date-parts":[[2012,1,17]],"date-time":"2012-01-17T07:29:07Z","timestamp":1326785347000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["IFN-gamma signaling in the central nervous system controls the course of experimental autoimmune encephalomyelitis independently of the localization and composition of inflammatory foci"],"prefix":"10.1186","volume":"9","author":[{"given":"Eunyoung","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Chanamara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pleasure","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena M","family":"Soulika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,1,16]]},"reference":[{"key":"510_CR1_510","doi-asserted-by":"publisher","first-page":"14965","DOI":"10.1523\/JNEUROSCI.3794-09.2009","volume":"29","author":"AM Soulika","year":"2009","unstructured":"Soulika AM, Lee E, McCauley E, Miers L, Bannerman P, Pleasure D: Initiation and Progression of Axonopathy in Experimental Autoimmune Encephalomyelitis. Journal of Neuroscience 2009, 29:14965\u201314979.","journal-title":"Journal of Neuroscience"},{"key":"510_CR2_510","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/S1474-4422(09)70043-2","volume":"8","author":"BD Trapp","year":"2009","unstructured":"Trapp BD, Stys PK: Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol 2009, 8:280\u2013291.","journal-title":"Lancet Neurol"},{"key":"510_CR3_510","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1177\/135245859900500205","volume":"5","author":"DW Langdon","year":"1999","unstructured":"Langdon DW, Thompson AJ: Multiple sclerosis: a preliminary study of selected variables affecting rehabilitation outcome. Multiple Sclerosis 1999, 5:94\u2013100.","journal-title":"Multiple Sclerosis"},{"key":"510_CR4_510","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1177\/1352458506070923","volume":"12","author":"RT Naismith","year":"2006","unstructured":"Naismith RT, Trinkaus K, Cross AH: Phenotype and prognosis in African-Americans with multiple sclerosis: a retrospective chart review. Multiple Sclerosis 2006, 12:775\u2013781.","journal-title":"Multiple Sclerosis"},{"key":"510_CR5_510","volume-title":"Journal of Neurology","author":"W Zaaraoui","year":"2010","unstructured":"Zaaraoui W, Reuter F, Rico A, Faivre A, Crespy L, Malikova I, Soulier E, Viout P, Le Fur Y, Confort-Gouny S, et al.: Occurrence of neuronal dysfunction during the first 5 years of multiple sclerosis is associated with cognitive deterioration. Journal of Neurology 2010."},{"key":"510_CR6_510","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1146\/annurev.immunol.15.1.749","volume":"15","author":"U Boehm","year":"1997","unstructured":"Boehm U, Klamp T, Groot M, Howard JC: Cellular responses to interferon-gamma. Annual Review of Immunology 1997, 15:749\u2013795.","journal-title":"Annual Review of Immunology"},{"key":"510_CR7_510","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1146\/annurev.iy.11.040193.003035","volume":"11","author":"MA Farrar","year":"1993","unstructured":"Farrar MA, Schreiber RD: The Molecular Cell Biology of Interferon-Gamma and Its Receptor. Annual Review of Immunology 1993, 11:571\u2013611.","journal-title":"Annual Review of Immunology"},{"key":"510_CR8_510","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1084\/jem.186.12.2023","volume":"186","author":"H Neumann","year":"1997","unstructured":"Neumann H, Schmidt H, Wilharm E, Behrens L, Wekerle H: Interferon gamma gene expression in sensory neurons: Evidence for autocrine gene regulation. Journal of Experimental Medicine 1997, 186:2023\u20132031.","journal-title":"Journal of Experimental Medicine"},{"key":"510_CR9_510","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.bbi.2009.09.016","volume":"24","author":"L Sun","year":"2010","unstructured":"Sun L, Tian ZZ, Wang JP: A direct cross-talk between interferon-gamma and sonic hedgehog signaling that leads to the proliferation of neuronal precursor cells. Brain Behavior and Immunity 2010, 24:220\u2013228.","journal-title":"Brain Behavior and Immunity"},{"key":"510_CR10_510","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.it.2008.07.002","volume":"29","author":"H Kelchtermans","year":"2008","unstructured":"Kelchtermans H, Billiau A, Matthys P: How interferon-gamma keeps autoimmune diseases in check. Trends Immunol 2008, 29:479\u2013486.","journal-title":"Trends Immunol"},{"key":"510_CR11_510","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1016\/S1567-5769(03)00131-0","volume":"3","author":"H Muhl","year":"2003","unstructured":"Muhl H, Pfeilschifter J: Anti-inflammatory properties of pro-inflammatory interferon-gamma. Int Immunopharmacol 2003, 3:1247\u20131255.","journal-title":"Int Immunopharmacol"},{"key":"510_CR12_510","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1084\/jem.192.1.123","volume":"192","author":"CQ Chu","year":"2000","unstructured":"Chu CQ, Wittmer S, Dalton DK: Failure to suppress the expansion of the activated CD4 T cell population in interferon gamma-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis. Journal of Experimental Medicine 2000, 192:123\u2013128.","journal-title":"Journal of Experimental Medicine"},{"key":"510_CR13_510","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1084\/jem.192.1.117","volume":"192","author":"DK Dalton","year":"2000","unstructured":"Dalton DK, Haynes L, Chu CQ, Swain SL, Wittmer S: Interferon gamma eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells. Journal of Experimental Medicine 2000, 192:117\u2013122.","journal-title":"Journal of Experimental Medicine"},{"key":"510_CR14_510","first-page":"2434","volume":"116","author":"ZJ Wang","year":"2006","unstructured":"Wang ZJ, Hong J, Sun W, Xu GW, Li NL, Chen X, Liu A, Xu LY, Sun B, Zhang JWZ: Role of IFN-gamma in induction of Foxp3 and conversion of CD4(+)CD25(-) T cells to CD4(+) Tregs. Journal of Clinical Investigation 2006, 116:2434\u20132441.","journal-title":"Journal of Clinical Investigation"},{"key":"510_CR15_510","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1016\/j.neurobiolaging.2008.02.019","volume":"30","author":"S Hashioka","year":"2009","unstructured":"Hashioka S, Klegeris A, Schwab C, McGeer PL: Interferon-gamma-dependent cytotoxic activation of human astrocytes and astrocytoma cells. Neurobiology of Aging 2009, 30:1924\u20131935.","journal-title":"Neurobiology of Aging"},{"key":"510_CR16_510","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/BF02740619","volume":"14","author":"B Popko","year":"1997","unstructured":"Popko B, Corbin JG, Baerwald KD, Dupree J, Garcia AM: The effects of interferon-gamma on the central nervous system. Molecular Neurobiology 1997, 14:19\u201335.","journal-title":"Molecular Neurobiology"},{"key":"510_CR17_510","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/0165-5728(91)90166-5","volume":"35","author":"N Rubio","year":"1991","unstructured":"Rubio N, Defelipe C: Demonstration of the Presence of a Specific Interferon-Gamma Receptor on Murine Astrocyte Cell-Surface. Journal of Neuroimmunology 1991, 35:111\u2013117.","journal-title":"Journal of Neuroimmunology"},{"key":"510_CR18_510","first-page":"250","volume":"86","author":"C Torres","year":"1995","unstructured":"Torres C, Aranguez I, Rubio N: Expression of Interferon-Gamma Receptors on Murine Oligodendrocytes and Its Regulation by Cytokines and Mitogens. Immunology 1995, 86:250\u2013255.","journal-title":"Immunology"},{"key":"510_CR19_510","doi-asserted-by":"publisher","first-page":"8032","DOI":"10.1073\/pnas.0810420106","volume":"106","author":"M Tsuda","year":"2009","unstructured":"Tsuda M, Masuda T, Kitano J, Shimoyama H, Tozaki-Saitoh H, Inoue K: IFN-gamma receptor signaling mediates spinal microglia activation driving neuropathic pain. Proceedings of the National Academy of Sciences of the United States of America 2009, 106:8032\u20138037.","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"510_CR20_510","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1023\/A:1006903002044","volume":"27","author":"K Vikman","year":"1998","unstructured":"Vikman K, Robertson B, Grant G, Liljeborg A, Kristensson K: Interferon-gamma receptors are expressed at synapses in the rat superficial dorsal horn and lateral spinal nucleus. Journal of Neurocytology 1998, 27:749\u2013759.","journal-title":"Journal of Neurocytology"},{"key":"510_CR21_510","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.4049\/jimmunol.140.5.1506","volume":"140","author":"A Billiau","year":"1988","unstructured":"Billiau A, Heremans H, Vandekerckhove F, Dijkmans R, Sobis H, Meulepas E, Carton H: Enhancement of Experimental Allergic Encephalomyelitis in Mice by Antibodies against Ifn-Gamma. Journal of Immunology 1988, 140:1506\u20131510.","journal-title":"Journal of Immunology"},{"key":"510_CR22_510","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.4049\/jimmunol.167.3.1821","volume":"167","author":"R Furlan","year":"2001","unstructured":"Furlan R, Brambilla E, Ruffini F, Poliani PL, Bergami A, Marconi PC, Franciotta DM, Penna G, Comi G, Adorini L, Martino G: Intrathecal delivery of IFN-gamma protects C57BL\/6 mice from chronic-progressive experimental autoimmune encephalomyelitis by increasing apoptosis of central nervous system-infiltrating lymphocytes. Journal of Immunology 2001, 167:1821\u20131829.","journal-title":"Journal of Immunology"},{"key":"510_CR23_510","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1111\/j.1365-2249.1990.tb03315.x","volume":"81","author":"JA Voorthuis","year":"1990","unstructured":"Voorthuis JA, Uitdehaag BM, De Groot CJ, Goede PH, van der Meide PH, Dijkstra CD: Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats. Clin Exp Immunol 1990, 81:183\u2013188.","journal-title":"Clin Exp Immunol"},{"key":"510_CR24_510","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1084\/jem.20080155","volume":"205","author":"JR Lees","year":"2008","unstructured":"Lees JR, Golumbek PT, Sim J, Dorsey D, Russell JH: Regional CNS responses to IFN-gamma determine lesion localization patterns during EAE pathogenesis. Journal of Experimental Medicine 2008, 205:2633\u20132642.","journal-title":"Journal of Experimental Medicine"},{"key":"510_CR25_510","doi-asserted-by":"crossref","first-page":"5278","DOI":"10.4049\/jimmunol.163.10.5278","volume":"163","author":"DO Willenborg","year":"1999","unstructured":"Willenborg DO, Fordham SA, Staykova MA, Ramshaw IA, Cowden WB: IFN-gamma is critical to the control of murine autoimmune encephalomyelitis and regulates both in the periphery and in the target tissue: A possible role for nitric oxide. Journal of Immunology 1999, 163:5278\u20135286.","journal-title":"Journal of Immunology"},{"key":"510_CR26_510","doi-asserted-by":"publisher","first-page":"8066","DOI":"10.4049\/jimmunol.180.12.8066","volume":"180","author":"JR Lees","year":"2008","unstructured":"Lees JR, Iwakura Y, Russell JH: Host T cells are the main producers of IL-17 within the central nervous system during initiation of experimental autoimmune encephalomyelitis of Th1 cell lines. Journal of Immunology 2008, 180:8066\u20138072.","journal-title":"Journal of Immunology"},{"key":"510_CR27_510","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/0165-5728(93)90240-Y","volume":"46","author":"DS Skundric","year":"1993","unstructured":"Skundric DS, Kim C, Tse HY, Raine CS: Homing of T cells to the central nervous system throughout the course of relapsing experimental autoimmune encephalomyelitis in Thy-1 congenic mice. Journal of Neuroimmunology 1993, 46:113\u2013121.","journal-title":"Journal of Neuroimmunology"},{"key":"510_CR28_510","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jneuroim.2007.06.016","volume":"189","author":"S Kuerten","year":"2007","unstructured":"Kuerten S, Kostova-Bales DA, Frenzel LP, Tigno JT, Tary-Lehmann M, Angelov DN, Lehmann PV: MP4- and MOG:35\u201355-induced EAE in C57BL\/6 mice differentially targets brain, spinal cord and cerebellum. Journal of Neuroimmunology 2007, 189:31\u201340.","journal-title":"Journal of Neuroimmunology"},{"key":"510_CR29_510","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1080\/147342202753203096","volume":"1","author":"JR Tonra","year":"2002","unstructured":"Tonra JR: Cerebellar susceptibility to experimental autoimmune encephalomyelitis in SJL\/J mice: potential interaction of immunology with vascular anatomy. Cerebellum 2002, 1:57\u201368.","journal-title":"Cerebellum"},{"key":"510_CR30_510","doi-asserted-by":"publisher","first-page":"3376","DOI":"10.1002\/jnr.22488","volume":"88","author":"JZ Zheng","year":"2010","unstructured":"Zheng JZ, Bizzozero OA: Accumulation of Protein Carbonyls Within Cerebellar Astrocytes in Murine Experimental Autoimmune Encephalomyelitis. Journal of Neuroscience Research 2010, 88:3376\u20133385.","journal-title":"Journal of Neuroscience Research"},{"key":"510_CR31_510","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1002\/glia.20437","volume":"55","author":"P Bannerman","year":"2007","unstructured":"Bannerman P, Hahn A, Soulika A, Gallo V, Pleasure D: Astrogliosis in EAE spinal cord: Derivation from radial glia, and relationships to oligodendroglia. Glia 2007, 55:57\u201364.","journal-title":"Glia"},{"key":"510_CR32_510","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1016\/S0002-9440(10)63410-4","volume":"165","author":"S Abromson-Leeman","year":"2004","unstructured":"Abromson-Leeman S, Bronson R, Luo Y, Berman M, Leeman R, Leeman J, Dorf M: T-cell properties determine disease site, clinical presentation, and cellular pathology of experimental autoimmune encephalomyelitis. American Journal of Pathology 2004, 165:1519\u20131533.","journal-title":"American Journal of Pathology"},{"key":"510_CR33_510","doi-asserted-by":"publisher","first-page":"2759","DOI":"10.4049\/jimmunol.164.5.2759","volume":"164","author":"EH Tran","year":"2000","unstructured":"Tran EH, Prince EN, Owens T: IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines. Journal of Immunology 2000, 164:2759\u20132768.","journal-title":"Journal of Immunology"},{"key":"510_CR34_510","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.immuni.2010.08.018","volume":"33","author":"V Siffrin","year":"2010","unstructured":"Siffrin V, Radbruch H, Glumm R, Niesner R, Paterka M, Herz J, Leuenberger T, Lehmann SM, Luenstedt S, Rinnenthal JL, et al.: In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 2010, 33:424\u2013436.","journal-title":"Immunity"},{"key":"510_CR35_510","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1084\/jem.20090299","volume":"206","author":"B Pollinger","year":"2009","unstructured":"Pollinger B, Krishnamoorthy G, Berer K, Lassmann H, Bosl MR, Dunn R, Domingues HS, Holz A, Kurschus FC, Wekerle H: Spontaneous relapsing-remitting EAE in the SJL\/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells. Journal of Experimental Medicine 2009, 206:1303\u20131316.","journal-title":"Journal of Experimental Medicine"},{"key":"510_CR36_510","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1002\/eji.1830180725","volume":"18","author":"A De la Hera","year":"1988","unstructured":"De la Hera A, Alvarez-Mon M, Sanchez-Madrid F, Martinez C, Durantez A: Co-expression of Mac-1 and p150,95 on CD5+ B cells. Structural and functional characterization in a human chronic lymphocytic leukemia. European Journal of Immunology 1988, 18:1131\u20131134.","journal-title":"European Journal of Immunology"},{"key":"510_CR37_510","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.4049\/jimmunol.149.4.1326","volume":"149","author":"HI McFarland","year":"1992","unstructured":"McFarland HI, Nahill SR, Maciaszek JW, Welsh RM: CD11b (Mac-1): a marker for CD8+ cytotoxic T cell activation and memory in virus infection. Journal of Immunology 1992, 149:1326\u20131333.","journal-title":"Journal of Immunology"},{"key":"510_CR38_510","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1002\/eji.1830090410","volume":"9","author":"T Springer","year":"1979","unstructured":"Springer T, Galfre G, Secher DS, Milstein C: Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. European Journal of Immunology 1979, 9:301\u2013306.","journal-title":"European Journal of Immunology"},{"key":"510_CR39_510","doi-asserted-by":"publisher","first-page":"5699","DOI":"10.1073\/pnas.80.18.5699","volume":"80","author":"SD Wright","year":"1983","unstructured":"Wright SD, Rao PE, Van Voorhis WC, Craigmyle LS, Iida K, Talle MA, Westberg EF, Goldstein G, Silverstein SC: Identification of the C3bi receptor of human monocytes and macrophages by using monoclonal antibodies. Proc Natl Acad Sci USA 1983, 80:5699\u20135703.","journal-title":"Proc Natl Acad Sci USA"},{"key":"510_CR40_510","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/288394a0","volume":"288","author":"JM Zarling","year":"1980","unstructured":"Zarling JM, Kung PC: Monoclonal antibodies which distinguish between human NK cells and cytotoxic T lymphocytes. Nature 1980, 288:394\u2013396.","journal-title":"Nature"},{"key":"510_CR41_510","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/BF03033380","volume":"5","author":"C Bjartmar","year":"2003","unstructured":"Bjartmar C, Trapp BD: Axonal degeneration and progressive neurologic disability in multiple sclerosis. Neurotox Res 2003, 5:157\u2013164.","journal-title":"Neurotox Res"},{"key":"510_CR42_510","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0022-510X(02)00069-2","volume":"206","author":"C Bjartmar","year":"2003","unstructured":"Bjartmar C, Wujek JR, Trapp BD: Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease. J Neurol Sci 2003, 206:165\u2013171.","journal-title":"J Neurol Sci"},{"key":"510_CR43_510","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/cne.901140104","volume":"114","author":"MB Carpenter","year":"1960","unstructured":"Carpenter MB, Alling FA, Bard DS: Lesions of the Descending Vestibular Nucleus in the Cat. Journal of Comparative Neurology 1960, 114:39.","journal-title":"Journal of Comparative Neurology"},{"key":"510_CR44_510","doi-asserted-by":"publisher","first-page":"999","DOI":"10.2353\/ajpath.2006.050791","volume":"169","author":"LP Shriver","year":"2006","unstructured":"Shriver LP, Dittel BN: T-cell-mediated disruption of the neuronal microtubule network: correlation with early reversible axonal dysfunction in acute experimental autoimmune encephalomyelitis. American Journal of Pathology 2006, 169:999\u20131011.","journal-title":"American Journal of Pathology"},{"key":"510_CR45_510","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.jneuroim.2007.09.031","volume":"192","author":"S Abromson-Leeman","year":"2007","unstructured":"Abromson-Leeman S, Ladell DS, Bronson RT, Dorf ME: Heterogeneity of EAE mediated by multiple distinct T-effector subsets. Journal of Neuroimmunology 2007, 192:3\u201312.","journal-title":"Journal of Neuroimmunology"},{"key":"510_CR46_510","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1084\/jem.20031819","volume":"200","author":"E Bettelli","year":"2004","unstructured":"Bettelli E, Sullivan B, Szabo SJ, Sobel RA, Glimcher LH, Kuchroo VK: Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. Journal of Experimental Medicine 2004, 200:79\u201387.","journal-title":"Journal of Experimental Medicine"},{"key":"510_CR47_510","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nm1715","volume":"14","author":"IM Stromnes","year":"2008","unstructured":"Stromnes IM, Cerretti LM, Liggitt D, Harris RA, Goverman JM: Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nature Medicine 2008, 14:337\u2013342.","journal-title":"Nature Medicine"},{"key":"510_CR48_510","doi-asserted-by":"publisher","first-page":"9780","DOI":"10.1128\/JVI.75.20.9780-9789.2001","volume":"75","author":"JK Olson","year":"2001","unstructured":"Olson JK, Girvin AM, Miller SD: Direct activation of innate and antigen-presenting functions of microglia following infection with Theiler's virus. J Virol 2001, 75:9780\u20139789.","journal-title":"J Virol"},{"key":"510_CR49_510","doi-asserted-by":"publisher","first-page":"5965","DOI":"10.1523\/JNEUROSCI.0060-08.2008","volume":"28","author":"J Neumann","year":"2008","unstructured":"Neumann J, Sauerzweig S, Roenicke R, Gunzer F, Dinkel K, Ullrich O, Gunzer M, Reymann KG: Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: A new mechanism of CNS immune privilege. Journal of Neuroscience 2008, 28:5965\u20135975.","journal-title":"Journal of Neuroscience"},{"key":"510_CR50_510","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1002\/glia.10154","volume":"40","author":"WJ Streit","year":"2002","unstructured":"Streit WJ: Microglia as neuroprotective, immunocompetent cells of the CNS. Glia 2002, 40:133\u2013139.","journal-title":"Glia"},{"key":"510_CR51_510","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1002\/glia.20419","volume":"54","author":"NM Walton","year":"2006","unstructured":"Walton NM, Sutter BM, Laywell ED, Levkoff LH, Kearns SM, Marshall GP, Scheffler B, Steindler DA: Microglia instruct subventricular zone neurogenesis. Glia 2006, 54:815\u2013825.","journal-title":"Glia"},{"key":"510_CR52_510","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/nn1629","volume":"9","author":"Y Ziv","year":"2006","unstructured":"Ziv Y, Ron N, Butovsky O, Landa G, Sudai E, Greenberg N, Cohen H, Kipnis J, Schwartz M: Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood. Nature Neuroscience 2006, 9:268\u2013275.","journal-title":"Nature Neuroscience"},{"key":"510_CR53_510","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1096\/fj.03-0670fje","volume":"18","author":"AI Iliev","year":"2004","unstructured":"Iliev AI, Stringaris AK, Nau R, Neumann H: Neuronal injury mediated via stimulation of microglial toll-like receptor-9 (TLR9). Faseb Journal 2004, 18:412\u2013414.","journal-title":"Faseb Journal"},{"key":"510_CR54_510","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1523\/JNEUROSCI.5643-07.2008","volume":"28","author":"V Kaushal","year":"2008","unstructured":"Kaushal V, Schlichter LC: Mechanisms of microglia-mediated neurotoxicity in a new model of the stroke penumbra. Journal of Neuroscience 2008, 28:2221\u20132230.","journal-title":"Journal of Neuroscience"},{"key":"510_CR55_510","first-page":"318","volume":"962","author":"B Liu","year":"2002","unstructured":"Liu B, Gao HM, Wang JY, Jeohn GH, Cooper CL, Hong JS: Role of nitric oxide in inflammation-mediated neurodegeneration. Nitric Oxide: Novel Actions, Deleterious Effects and Clinical Potential 2002, 962:318\u2013331.","journal-title":"Nitric Oxide: Novel Actions, Deleterious Effects and Clinical Potential"},{"key":"510_CR56_510","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nm.2324","volume":"17","author":"I Nikic","year":"2011","unstructured":"Nikic I, Merkler D, Sorbara C, Brinkoetter M, Kreutzfeldt M, Bareyre FM, Bruck W, Bishop D, Misgeld T, Kerschensteiner M: A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis. Nature Medicine 2011, 17:495-U135.","journal-title":"Nature Medicine"},{"key":"510_CR57_510","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/nrn2023","volume":"7","author":"SG Waxman","year":"2006","unstructured":"Waxman SG: Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nature Reviews Neuroscience 2006, 7:932\u2013941.","journal-title":"Nature Reviews Neuroscience"},{"key":"510_CR58_510","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.neulet.2010.07.077","volume":"483","author":"D Maskey","year":"2010","unstructured":"Maskey D, Pradhan J, Kim HJ, Park KS, Ahn SC, Kim MJ: Immunohistochemical localization of calbindin D28-k, parvalbumin, and calretinin in the cerebellar cortex of the circling mouse. Neuroscience Letters 2010, 483:132\u2013136.","journal-title":"Neuroscience Letters"}],"updated-by":[{"DOI":"10.1186\/s12974-016-0702-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T00:00:00Z","timestamp":1472515200000}}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1742-2094-9-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/1742-2094-9-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1742-2094-9-7","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1742-2094-9-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T17:57:30Z","timestamp":1686679050000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/1742-2094-9-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,16]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["510"],"URL":"https:\/\/doi.org\/10.1186\/1742-2094-9-7","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,16]]},"assertion":[{"value":"16 July 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"510"}}