{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:52:13Z","timestamp":1785199933813,"version":"3.55.0"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T00:00:00Z","timestamp":1550448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473577"],"award-info":[{"award-number":["81473577"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81501032"],"award-info":[{"award-number":["81501032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Multiple sclerosis (MS) is a relapsing\u2010remitting inflammatory demyelinating disease that requires long\u2010term treatment. Although Rho kinase inhibitor Fasudil shows good therapeutic effect in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, certain side effects may limit its clinical use. This study aimed at observing the therapeutic potential of Fasudil\u2010modified encephalitogenic mononuclear cells (MNCs) via nasal delivery in EAE and exploring possible mechanisms of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Experimental autoimmune encephalomyelitis was induced with myelin oligodendrocyte glycoprotein 35\u201055 in C57BL\/6 mice, and encephalitogenic MNCs were treated with Fasudil in vitro. Mice received 3\u00a0\u00d7\u00a010<jats:sup>6<\/jats:sup>\u00a0cells\/10\u00a0\u03bcL per nasal cavity on day 3 and 11 postimmunization, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fasudil\u2010modified MNCs reduced clinical severity of EAE, improved demyelination, and decreased inflammatory cells in spinal cords. Immunohistochemical results indicated that CD4<jats:sup>+<\/jats:sup> T cells and CD68<jats:sup>+<\/jats:sup> macrophages were barely detected in Fasudil\u2010MNCs group. Fasudil\u2010modified MNCs decreased CD4<jats:sup>+<\/jats:sup>IFN\u2010\u03b3<jats:sup>+<\/jats:sup> and CD4<jats:sup>+<\/jats:sup>IL\u201017<jats:sup>+<\/jats:sup> T cells, increased CD4<jats:sup>+<\/jats:sup>IL\u201010<jats:sup>+<\/jats:sup> T cells, restrained M1 markers CD16\/32, CCR7, IL\u201012, CD8a, enhanced M2 markers CD206, CD200, CD14 in spleen. Fasudil\u2010modified MNCs inhibited the activation of inflammatory signaling p\u2010NF\u2010kB\/P38, accompanied by the decrease of COX\u20102 and the increase of Arg\u20101 in spinal cord, as well as the reduction of IL\u201017, TNF\u2010\u03b1, IL\u20106 and the elevation of IL\u201010 in cultured supernatant of splenocytes. Fasudil\u2010modified MNCs enhanced the levels of neurotrophic factors BDNF and NT\u20103 in spinal cord.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that intranasal delivery of Fasudil\u2010modified MNCs have therapeutic potential in EAE, providing a safe and effective cell therapeutic strategy to MS and\/or other related disorders.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13111","type":"journal-article","created":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T05:12:12Z","timestamp":1550553132000},"page":"783-795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Nasal delivery of Fasudil\u2010modified immune cells exhibits therapeutic potential in experimental autoimmune encephalomyelitis"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8011-3747","authenticated-orcid":false,"given":"Shang\u2010De","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurology, Institute of Brain Science, Medical School Shanxi Datong University Datong China"},{"name":"Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science Shanxi Datong University Datong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Yun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Brain Science, Medical School Shanxi Datong University Datong China"},{"name":"Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science Shanxi Datong University Datong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Wen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Brain Science, Medical School Shanxi Datong University Datong China"},{"name":"Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science Shanxi Datong University Datong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Chai","sequence":"additional","affiliation":[{"name":"Research Center of Neurobiology Shanxi University of Traditional Chinese Medicine Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center of Neurobiology Shanxi University of Traditional Chinese Medicine Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi\u2010Ting","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Brain Science, Medical School Shanxi Datong University Datong China"},{"name":"Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science Shanxi Datong University Datong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Bin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Brain Science, Medical School Shanxi Datong University Datong China"},{"name":"Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science Shanxi Datong University Datong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Brain Science, Medical School Shanxi Datong University Datong China"},{"name":"Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science Shanxi Datong University Datong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng\u2010Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Center of Neurobiology Shanxi University of Traditional Chinese Medicine Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Brain Science, Medical School Shanxi Datong University Datong China"},{"name":"Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science Shanxi Datong University Datong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3335-8992","authenticated-orcid":false,"given":"Bao\u2010Guo","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Neurology Huashan Hospital Institutes of Brain Science and State Key Laboratory of Medical Neurobiology Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cun\u2010Gen","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Institute of Brain Science, Medical School Shanxi Datong University Datong China"},{"name":"Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Institute of Brain Science Shanxi Datong University Datong China"},{"name":"Research Center of Neurobiology Shanxi University of Traditional Chinese Medicine Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206093109"},{"key":"e_1_2_8_3_1","first-page":"249101","article-title":"Current and future therapies for multiple sclerosis","volume":"13","author":"Minagar A","year":"2013","journal-title":"Scientifica (Cairo)"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13349"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2017.10.007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"75038","DOI":"10.18632\/oncotarget.20500","article-title":"Immethridine, histamine H3\u2010receptor (H3R) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells","volume":"8","author":"Shi Y","year":"2017","journal-title":"Oncotarget"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00382"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201445422"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.11.002"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.02.015"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2014.03.006"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-03-0200"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-014-0411-7"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0027-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12116"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527315666160711104719"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054841"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12002"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20150032"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-012-0915-1"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1423173"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-016-0819-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344429"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(99)00139-3"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12880"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.03.011"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368914X684970"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.12.025"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12303"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1159\/000321044"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.02.001"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2009.11.019"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000351221"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-20390-5"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2013.08.008"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-011-0352-3"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(98)00257-4"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2007.07.012"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.04.013"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00050"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2017.11"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/08820139.2016.1208216"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2015.11.011"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570161113666150923111329"},{"key":"e_1_2_8_46_1","first-page":"211","article-title":"Fatigue in patients with multiple sclerosis\u2013pathogenesis, clinical picture, diagnosis and treatment","volume":"83","author":"Patejdl R","year":"2015","journal-title":"Fortschr Neurol Psychiatr"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-15"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1608-17.2017"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2016.12.020"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.338541"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24020"},{"key":"e_1_2_8_52_1","first-page":"274","article-title":"Cytokine signaling in multiple sclerosis and its therapeutic applications","volume":"5","author":"Palle P","year":"2017","journal-title":"Med Sci"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-05-01633.1998"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-336552"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201000103"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0487-18.2018"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2016.05.028"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03592-1"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.205084"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.006692"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1039\/c4ib00009a"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.241"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcns.13111","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T10:23:03Z","timestamp":1694341383000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.13111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,18]]},"references-count":61,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1111\/cns.13111"],"URL":"https:\/\/doi.org\/10.1111\/cns.13111","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,18]]},"assertion":[{"value":"2018-07-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}