{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:33:30Z","timestamp":1787240010314,"version":"build-2736575974"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T00:00:00Z","timestamp":1515369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T00:00:00Z","timestamp":1515369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neuromyelitis optica (NMO) is an autoimmune disease associated with NMO immunoglobulin G (NMO-IgG), an antibody that selectively binds to the aquaporin-4. Here, we established a localized NMO model by injecting NMO-IgG into the spinal cord, and assessed the efficacy of treating its NMO-like symptoms by blocking repulsive guidance molecule-a (RGMa), an axon growth inhibitor. The model showed pathological features consistent with NMO. Systemic administration of humanized monoclonal anti-RGMa antibody delayed the onset and attenuated the severity of clinical symptoms. Further, it preserved astrocytes and reduced inflammatory-cell infiltration and axonal damage, suggesting that targeting RGMa is effective in treating NMO.<\/jats:p>","DOI":"10.1038\/s41598-017-18362-2","type":"journal-article","created":{"date-parts":[[2018,1,2]],"date-time":"2018-01-02T10:25:47Z","timestamp":1514888747000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Inhibition of RGMa alleviates symptoms in a rat model of neuromyelitis optica"],"prefix":"10.1038","volume":"8","author":[{"given":"Kana","family":"Harada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsusada","family":"Okuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Tanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Koyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0874-7542","authenticated-orcid":false,"given":"Hideki","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,8]]},"reference":[{"key":"18362_CR1","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/S1474-4422(07)70216-8","volume":"6","author":"DM Wingerchuk","year":"2007","unstructured":"Wingerchuk, D. M., Lennon, V. A., Lucchinetti, C. F., Pittock, S. J. & Weinshenker, B. G. The spectrum of neuromyelitis optica. Lancet Neurol 6, 805\u2013815, https:\/\/doi.org\/10.1016\/S1474-4422(07)70216-8 (2007).","journal-title":"Lancet Neurol"},{"key":"18362_CR2","doi-asserted-by":"publisher","unstructured":"Flanagan, E. P. et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol, https:\/\/doi.org\/10.1002\/ana.24617 (2016).","DOI":"10.1002\/ana.24617"},{"key":"18362_CR3","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1016\/S0140-6736(04)17551-X","volume":"364","author":"VA Lennon","year":"2004","unstructured":"Lennon, V. A. et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364, 2106\u20132112, https:\/\/doi.org\/10.1016\/S0140-6736(04)17551-X (2004).","journal-title":"Lancet"},{"key":"18362_CR4","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1084\/jem.20050304","volume":"202","author":"VA Lennon","year":"2005","unstructured":"Lennon, V. A., Kryzer, T. J., Pittock, S. J., Verkman, A. S. & Hinson, S. R. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202, 473\u2013477, https:\/\/doi.org\/10.1084\/jem.20050304 (2005).","journal-title":"J Exp Med"},{"key":"18362_CR5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.tins.2007.11.003","volume":"31","author":"MJ Tait","year":"2008","unstructured":"Tait, M. J., Saadoun, S., Bell, B. A. & Papadopoulos, M. C. Water movements in the brain: role of aquaporins. Trends Neurosci 31, 37\u201343, https:\/\/doi.org\/10.1016\/j.tins.2007.11.003 (2008).","journal-title":"Trends Neurosci"},{"key":"18362_CR6","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1002\/ana.21837","volume":"66","author":"M Bradl","year":"2009","unstructured":"Bradl, M. et al. Neuromyelitis optica: pathogenicity of patient immunoglobulin in vivo. Ann Neurol 66, 630\u2013643, https:\/\/doi.org\/10.1002\/ana.21837 (2009).","journal-title":"Ann Neurol"},{"key":"18362_CR7","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.bbrc.2009.06.085","volume":"386","author":"M Kinoshita","year":"2009","unstructured":"Kinoshita, M. et al. Neuromyelitis optica: Passive transfer to rats by human immunoglobulin. Biochem Biophys Res Commun 386, 623\u2013627, https:\/\/doi.org\/10.1016\/j.bbrc.2009.06.085 (2009).","journal-title":"Biochem Biophys Res Commun"},{"key":"18362_CR8","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/gene.2009.111","volume":"11","author":"R Nohra","year":"2010","unstructured":"Nohra, R. et al. RGMA and IL21R show association with experimental inflammation and multiple sclerosis. Genes Immun 11, 279\u2013293, https:\/\/doi.org\/10.1038\/gene.2009.111 (2010).","journal-title":"Genes Immun"},{"key":"18362_CR9","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1083\/jcb.200508143","volume":"173","author":"K Hata","year":"2006","unstructured":"Hata, K. et al. RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J Cell Biol 173, 47\u201358, https:\/\/doi.org\/10.1083\/jcb.200508143 (2006).","journal-title":"J Cell Biol"},{"key":"18362_CR10","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1001\/archneur.62.10.1561","volume":"62","author":"JM Schwab","year":"2005","unstructured":"Schwab, J. M. et al. Central nervous system injury-induced repulsive guidance molecule expression in the adult human brain. Arch Neurol 62, 1561\u20131568, https:\/\/doi.org\/10.1001\/archneur.62.10.1561 (2005).","journal-title":"Arch Neurol"},{"key":"18362_CR11","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1016\/j.celrep.2015.02.048","volume":"10","author":"E Demicheva","year":"2015","unstructured":"Demicheva, E. et al. Targeting repulsive guidance molecule A to promote regeneration and neuroprotection in multiple sclerosis. Cell Rep 10, 1887\u20131898, https:\/\/doi.org\/10.1016\/j.celrep.2015.02.048 (2015).","journal-title":"Cell Rep"},{"key":"18362_CR12","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1038\/nm.2321","volume":"17","author":"R Muramatsu","year":"2011","unstructured":"Muramatsu, R. et al. RGMa modulates T cell responses and is involved in autoimmune encephalomyelitis. Nat Med 17, 488\u2013494, https:\/\/doi.org\/10.1038\/nm.2321 (2011).","journal-title":"Nat Med"},{"key":"18362_CR13","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1016\/j.celrep.2014.10.038","volume":"9","author":"S Tanabe","year":"2014","unstructured":"Tanabe, S. & Yamashita, T. Repulsive guidance molecule-a is involved in Th17-cell-induced neurodegeneration in autoimmune encephalomyelitis. 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