{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:01:25Z","timestamp":1789736485851,"version":"4.0.1"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T00:00:00Z","timestamp":1426464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0121488","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T14:19:47Z","timestamp":1426515587000},"page":"e0121488","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":50,"title":["Fingolimod Prevents Blood-Brain Barrier Disruption Induced by the Sera from Patients with Multiple Sclerosis"],"prefix":"10.1371","volume":"10","author":[{"given":"Hideaki","family":"Nishihara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitaka","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuteru","family":"Sano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Takeshita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiaki","family":"Koga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,3,16]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1056\/NEJMoa052643","article-title":"Oral fingolimod (FTY720) for relapsing multiple sclerosis","volume":"355","author":"L Kappos","year":"2006","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"21453","DOI":"10.1074\/jbc.C200176200","article-title":"The immune modulator FTY720 targets sphingosine 1-phosphate receptors","volume":"277","author":"V Brinkmann","year":"2002","journal-title":"J Biol Chem"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1212\/WNL.0b013e31820db341","article-title":"Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis","volume":"76","author":"M Mehling","year":"2011","journal-title":"Neurology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1212\/WNL.0b013e31820d5ec1","article-title":"Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation","volume":"76","author":"T Hla","year":"2011","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/nrd3248","article-title":"Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis","volume":"9","author":"V Brinkmann","year":"2010","journal-title":"Nat Rev Drug Discov"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/WNF.0b013e3181cbf825","article-title":"Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis","volume":"33","author":"J Chun","year":"2010","journal-title":"Clin Neuropharmacol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1212\/WNL.0b013e31820d9507","article-title":"The neurobiology of sphingosine 1-phosphate signaling and sphingosine 1-phosphate receptor modulators","volume":"76","author":"B Soliven","year":"2011","journal-title":"Neurology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.2353\/ajpath.2008.080478","article-title":"Cyclical and dose-dependent responses of adult human mature oligodendrocytes to fingolimod","volume":"173","author":"VE Miron","year":"2008","journal-title":"Am J Pathol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"e92872","DOI":"10.1371\/journal.pone.0092872","article-title":"Sera from remitting and secondary progressive multiple sclerosis patients disrupt the blood-brain barrier","volume":"9","author":"F Shimizu","year":"2014","journal-title":"PLoS One"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/ana.22366","article-title":"Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria","volume":"69","author":"CH Polman","year":"2011","journal-title":"Ann Neurol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/jcp.22232","article-title":"Establishment of a new conditionally immortalized human brain microvascular endothelial cell line retaining an in vivo blood-brain barrier function","volume":"225","author":"Y Sano","year":"2010","journal-title":"J Cell Physiol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/cen3.12001","article-title":"Stable human brain microvascular endothelial cell line retaining its barrier-specific nature independent of the passage number","volume":"4","author":"Y Sano","year":"2013","journal-title":"Clin ExP Neuroimmunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1136\/jnnp-2011-300434","article-title":"Sera from neuromyelitis optica patients disrupt the blood-brain barrier","volume":"83","author":"F Shimizu","year":"2012","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/jcp.20676","article-title":"PPARgamma-regulated tight junction development during human urothelial cytodifferentiation","volume":"208","author":"CL Varley","year":"2006","journal-title":"J Cell Physiol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.bbrc.2012.04.005","article-title":"Nuclear IL-33 is a transcriptional regulator of NF-kappaB p65 and induces endothelial cell activation","volume":"421","author":"YS Choi","year":"2012","journal-title":"Biochem Biophys Res Commun"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.3748\/wjg.v12.i26.4241","article-title":"Expression of angiopoietins, Tie2 and vascular endothelial growth factor in angiogenesis and progression of hepatocellular carcinoma","volume":"12","author":"ZL Zhang","year":"2006","journal-title":"World J Gastroenterol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1136\/jnnp-2013-305907","article-title":"Autocrine MMP-2\/9 secretion increases the BBB permeability in neuromyelitis optica","volume":"85","author":"A Tasaki","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jns.2008.06.031","article-title":"Central nervous system-directed effects of FTY720 (fingolimod)","volume":"274","author":"VE Miron","year":"2008","journal-title":"J Neurol Sci"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1183\/09031936.00047810","article-title":"FTY720-induced human pulmonary endothelial barrier enhancement is mediated by c-Abl","volume":"38","author":"L Wang","year":"2011","journal-title":"Eur Respir J"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.brainresbull.2007.06.023","article-title":"FTY720 sustains and restores neuronal function in the DA rat model of MOG-induced experimental autoimmune encephalomyelitis","volume":"74","author":"B Balatoni","year":"2007","journal-title":"Brain Res Bull"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1750-3639.2008.00182.x","article-title":"FTY720 rescue therapy in the dark agouti rat model of experimental autoimmune encephalomyelitis: expression of central nervous system genes and reversal of blood-brain-barrier damage","volume":"19","author":"CA Foster","year":"2009","journal-title":"Brain Pathol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/ana.22186","article-title":"Fingolimod provides long-term protection in rodent models of cerebral ischemia","volume":"69","author":"Y Wei","year":"2011","journal-title":"Ann Neurol"},{"issue":"Pt 5","key":"ref23","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1093\/brain\/113.5.1477","article-title":"Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications","volume":"113","author":"AG Kermode","year":"1990","journal-title":"Brain"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1042\/BST0370329","article-title":"The effects of blood-brain barrier disruption on glial cell function in multiple sclerosis","volume":"37","author":"S McQuaid","year":"2009","journal-title":"Biochem Soc Trans"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1750-3639.2002.tb00430.x","article-title":"Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis","volume":"12","author":"J Plumb","year":"2002","journal-title":"Brain Pathol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/path.1434","article-title":"Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination","volume":"201","author":"J Kirk","year":"2003","journal-title":"J Pathol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/j.1365-2990.2006.00781.x","article-title":"Persistent endothelial abnormalities and blood-brain barrier leak in primary and secondary progressive multiple sclerosis","volume":"33","author":"S Leech","year":"2007","journal-title":"Neuropathol Appl Neurobiol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1212\/WNL.45.6_Suppl_6.S16","article-title":"Cytokine localization in multiple sclerosis lesions: correlation with adhesion molecule expression and reactive nitrogen species","volume":"45","author":"CF Brosnan","year":"1995","journal-title":"Neurology"},{"key":"ref29","author":"F Shimizu","year":"2013"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1600-065X.2012.01127.x","article-title":"Inflammatory cell trafficking across the blood-brain barrier: chemokine regulation and in vitro models","volume":"248","author":"Y Takeshita","year":"2012","journal-title":"Immunol Rev"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1759-1961.2010.009.x","article-title":"T cell migration into the central nervous system during health and disease: Different molecular keys allow access to different central nervous system compartments","volume":"1","author":"B Engelhardt","year":"2010","journal-title":"Clin ExP Neuroimmunol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nri2156","article-title":"Getting to the site of inflammation: the leukocyte adhesion cascade updated","volume":"7","author":"K Ley","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000109933","article-title":"Natalizumab: targeting alpha4-integrins in multiple sclerosis","volume":"5","author":"B Engelhardt","year":"2008","journal-title":"Neurodegener Dis"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1056\/NEJMoa0907839","article-title":"Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis","volume":"362","author":"JA Cohen","year":"2010","journal-title":"N Engl J Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/S1474-4422(11)70099-0","article-title":"Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study","volume":"10","author":"B Khatri","year":"2011","journal-title":"Lancet Neurol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1471-2377-14-21","article-title":"Fingolimod (FTY720) therapy in Japanese patients with relapsing multiple sclerosis over 12 months: results of a phase 2 observational extension","volume":"14","author":"J Kira","year":"2014","journal-title":"BMC Neurol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S1474-4422(14)70049-3","article-title":"Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial","volume":"13","author":"PA Calabresi","year":"2014","journal-title":"Lancet Neurol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJMoa0909494","article-title":"A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis","volume":"362","author":"L Kappos","year":"2010","journal-title":"N Engl J Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0121488","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T09:04:23Z","timestamp":1540199063000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0121488"}},"subtitle":[],"editor":[{"given":"Akio","family":"Suzumura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,3,16]]},"references-count":38,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0121488","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,16]]}}}