{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T21:34:44Z","timestamp":1784064884403,"version":"3.55.0"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2015BAI12B04"],"award-info":[{"award-number":["2015BAI12B04"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012401","name":"Beijing Science and Technology Planning Project","doi-asserted-by":"publisher","award":["D16110000381605"],"award-info":[{"award-number":["D16110000381605"]}],"id":[{"id":"10.13039\/501100012401","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009601","name":"Beijing Municipal Administration of Hospitals","doi-asserted-by":"publisher","award":["PX2016034"],"award-info":[{"award-number":["PX2016034"]}],"id":[{"id":"10.13039\/501100009601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009601","name":"Beijing Municipal Administration of Hospitals","doi-asserted-by":"publisher","award":["SML20150501"],"award-info":[{"award-number":["SML20150501"]}],"id":[{"id":"10.13039\/501100009601","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> This study was conducted in order to investigate the association of matrix metalloproteinase (MMP)-9 levels with phenotypes of moyamoya disease (MMD).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This study included plasma samples from 84 MMD patients. The clinical variables of these patients were reviewed from the medical record. The serum concentration of tight junction, adherens junction proteins, and MMPs (MMP-2 and MMP-9) was determined using the ELISA method. Patients with hemorrhagic-onset MMD were compared with those with ischemic-onset MMD.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Compared with pediatric patients, the expression of MMP-9 was significantly higher, while the MMP-2 and vascular endothelial-cadherin were lower in adult patients. In adult subgroup analysis, hemorrhagic MMD patients exhibited significantly higher serum concentrations of MMP-9 compared with ischemic MMD patients. The ROC curve identified that a baseline serum MMP-9 level &amp;gt;1,011 ng\/ml may be associated with spontaneous hemorrhage in adult MMD patients with 70.37% sensitivity and 71.88% specificity [area under curve (AUC), 0.73; 95% CI 0.597\u20130.864; <jats:italic>P<\/jats:italic> = 0.003]. A late Suzuki stage (&amp;gt;4) (OR 4.565, 95% CI 1.028\u201320.280, <jats:italic>P<\/jats:italic> = 0.046) and serum concentrations of MMP-9 &amp;gt;1,011 ng\/ml (OR 7.218, 95% CI 1.826\u201328.533, <jats:italic>P<\/jats:italic> = 0.005) are risk predictors of hemorrhages in MMD patients. Hemorrhagic-type MMD patients had higher serum levels of MMP-9 and BBB permeability compared with ischemic-type MMD patients. Adult MMD patients had higher serum levels of MMP-9 and BBB permeability compared with pediatric patients.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> MMP-9 might serve as a biomarker for hemorrhage prediction in MMD. Serum MMP-9 level &amp;gt;1,011 ng\/ml is an independent risk factor of MMD hemorrhagic strokes.<\/jats:p>","DOI":"10.3389\/fneur.2021.721118","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T20:31:46Z","timestamp":1630701106000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["MMP-9 as a Biomarker for Predicting Hemorrhagic Strokes in Moyamoya Disease"],"prefix":"10.3389","volume":"12","author":[{"given":"Junlin","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhidong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangchao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/S1474-4422(08)70240-0","article-title":"Moyamoya disease: current concepts and future perspectives","volume":"7","author":"Kuroda","year":"2008","journal-title":"Lancet Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1056\/NEJMra0804622","article-title":"Moyamoya disease and moyamoya syndrome","volume":"360","author":"Scott","year":"2009","journal-title":"N Engl J Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1161\/STROKEAHA.113.004386","article-title":"Effects of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease: results of the Japan Adult Moyamoya trial","volume":"45","author":"Miyamoto","year":"2014","journal-title":"Stroke."},{"key":"B4","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s00701-019-03811-w","article-title":"In vivo demonstration of blood-brain barrier impairment in Moyamoya disease","volume":"161","author":"Narducci","year":"2019","journal-title":"Acta Neurochir."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1007\/s00701-020-04480-w","article-title":"Decreased cortical perfusion in areas with blood-brain barrier dysfunction in Moyamoya disease","volume":"162","author":"Lu","year":"2020","journal-title":"Acta Neurochir."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.3389\/fneur.2018.01121","article-title":"Direct bypass surgery vs. combined bypass surgery for hemorrhagic moyamoya disease: a comparison of angiographic outcomes","volume":"9","author":"Zhao","year":"2018","journal-title":"Front Neurol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3171\/2018.9.JNS181562.","article-title":"Predictors of neoangiogenesis after indirect revascularization in moyamoya disease: a multicenter retrospective study","author":"Zhao","year":"2019","journal-title":"J Neurosurg"},{"key":"B8","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1002\/pro.5560040502","article-title":"The metzincins\u2013topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases) define a superfamily of zinc-peptidases","volume":"4","author":"Stocker","year":"1995","journal-title":"Protein Sci."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-021-05314-y.","article-title":"Expression pattern of matrix metalloproteinases-2 and\u22129 and their tissue inhibitors in patients with chronic inflammatory demyelinating polyneuropathy","author":"Cosentino","year":"2021","journal-title":"Neurol Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.jns.2006.11.021","article-title":"Elevation of matrix metalloproteinases (MMPs) in multiple sclerosis and impact of immunomodulators","volume":"259","author":"Yong","year":"2007","journal-title":"J Neurol Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1159\/000093870","article-title":"Serum levels of matrix metalloproteinases-2 and\u22129 and their tissue inhibitors in inflammatory neuromuscular disorders","volume":"55","author":"Hurnaus","year":"2006","journal-title":"Eur Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1177\/0271678X16655551","article-title":"Matrix metalloproteinases in the brain and blood-brain barrier: versatile breakers and makers","volume":"36","author":"Rempe","year":"2016","journal-title":"J Cereb Blood Flow Metab."},{"key":"B13","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1136\/jnnp.2009.191817","article-title":"Plasma matrix metalloproteinases, cytokines and angiogenic factors in moyamoya disease","volume":"81","author":"Kang","year":"2010","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1177\/0271678X18768443","article-title":"Gelatinolytic activity of autocrine matrix metalloproteinase-9 leads to endothelial de-arrangement in Moyamoya disease","volume":"38","author":"Blecharz-Lang","year":"2018","journal-title":"J Cereb Blood Flow Metab."},{"key":"B15","doi-asserted-by":"publisher","first-page":"245","DOI":"10.2176\/nmc.52.245","article-title":"Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of Willis)","volume":"52","year":"2012","journal-title":"Neurol Med Chir."},{"key":"B16","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1001\/archneur.1969.00480090076012","article-title":"Cerebrovascular \u201cmoyamoya\u201d disease. Disease showing abnormal net-like vessels in base of brain","volume":"20","author":"Suzuki","year":"1969","journal-title":"Arch Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1097\/WNR.0000000000000289","article-title":"Increased vascular MMP-9 in mice lacking RNF213: moyamoya disease susceptibility gene","volume":"25","author":"Sonobe","year":"2014","journal-title":"Neuroreport."},{"key":"B18","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.mam.2008.05.002","article-title":"Progress in matrix metalloproteinase research","volume":"29","author":"Murphy","year":"2008","journal-title":"Mol Aspects Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3124","DOI":"10.1161\/STROKEAHA.120.030653","article-title":"Association between the onset pattern of adult moyamoya disease and risk factors for stroke","volume":"51","author":"Hirano","year":"2020","journal-title":"Stroke."},{"key":"B20","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/bs.apha.2017.08.002","article-title":"Matrix metalloproteinases, vascular remodeling, and vascular disease","volume":"81","author":"Wang","year":"2018","journal-title":"Adv Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1002\/jcp.22175","article-title":"Expression profiling of ETS and MMP factors in VEGF-activated endothelial cells: role of MMP-10 in VEGF-induced angiogenesis","volume":"224","author":"Heo","year":"2010","journal-title":"J Cell Physiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.canlet.2009.11.002","article-title":"Increased endostatin generation and decreased angiogenesis via MMP-9 by tamoxifen in hormone dependent ovarian cancer","volume":"292","author":"Bendrik","year":"2010","journal-title":"Cancer Lett."},{"key":"B23","doi-asserted-by":"publisher","first-page":"4766","DOI":"10.1073\/pnas.0730882100","article-title":"Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins","volume":"100","author":"Sudhakar","year":"2003","journal-title":"Proc Natl Acad Sci USA."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.721118\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T20:31:49Z","timestamp":1630701109000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.721118\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":23,"alternative-id":["10.3389\/fneur.2021.721118"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.721118","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]},"article-number":"721118"}}