{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:36:39Z","timestamp":1792683399371,"version":"4.5.0"},"reference-count":34,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T00:00:00Z","timestamp":1475020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Inflammation in neuromyelitis optica (NMO) is triggered by a serum antibody against the aquaporin-4 (AQP4). This process requires antibody penetration of the blood\u2013brain barrier (BBB), but the mechanisms for BBB disruption in NMO remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We examined whether changes in cerebrospinal fluid (CSF) and serum matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and cytokines are associated with BBB disruption in NMO.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The concentrations 9 MMPs, 4 TIMPs, and 14 cytokines were measured by multiplex assay in CSF and serum samples from 29 NMO patients, 29 relapsing-remitting multiple sclerosis (MS) patients, and 27 patients with other neurological disorders. We also performed immunohistochemistry for MMP-2 and TIMP-1 expression in post-mortem brain tissues from NMO patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>NMO patients exhibited significantly elevated MMP-2, TIMP-1, interleukin-6, and MMP-2\/TIMP-2 ratio in CSF (but not sera) than the other groups. The CSF\/serum albumin ratio, an index of BBB permeability, was most strongly correlated with CSF MMP-2 concentration, which in turn correlated with CSF interleukin-6 levels. Immunohistochemistry revealed MMP-2- and TIMP-1-positive cells surrounding vessels in NMO lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In NMO, increased CSF MMP-2, likely induced by interleukin-6 signaling, may disrupt the BBB and enable serum anti-AQP-4 antibodies migration into the central nervous system (CNS).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1352458516672015","type":"journal-article","created":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T22:38:23Z","timestamp":1475102303000},"page":"1072-1084","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":57,"title":["Increased cerebrospinal fluid metalloproteinase-2 and interleukin-6 are associated with albumin quotient in neuromyelitis optica: Their possible role on blood\u2013brain barrier disruption"],"prefix":"10.1177","volume":"23","author":[{"given":"Tomohiko","family":"Uchida","sequence":"first","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyuki","family":"Uzawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, 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