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The expression levels and cellular specificity of the target genes of these mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s are unknown in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to analyze and validate the expression of mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s, previously reported as dysregulated in sera of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> patients, in white\u2010matter lesions (<jats:styled-content style=\"fixed-case\">WML<\/jats:styled-content>s) of progressive <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> brains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed global mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression profiling analysis in demyelinated <jats:styled-content style=\"fixed-case\">WML<\/jats:styled-content>s of progressive <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> brains (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) and compared the significantly altered mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s to previously identified mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s from sera of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> patients. Top dysregulated mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s common between the two datasets were validated in an independent cohort of <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> brains by quantitative <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>) and in\u00a0situ hybridization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s that were significantly changed in <jats:styled-content style=\"fixed-case\">WML<\/jats:styled-content> tissues, 11 were similar to pathogenic and 12 were common to protective mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s previously identified in sera and correlating with <jats:styled-content style=\"fixed-case\">WM MRI<\/jats:styled-content> abnormalities. Importantly, the expression levels of 58% of the protective mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s (7 of 12) were decreased in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> lesions compared to surrounding normal\u2010appearing tissue. Target genes of these mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s were also altered in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> lesions and queries of cell\u2010specific databases identified astrocytes and microglia as the key cellular expressers of these genes in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> brains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s that correlate with <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> abnormalities in lesioned tissue from <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> brains.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.750","type":"journal-article","created":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T04:09:12Z","timestamp":1553227752000},"page":"854-862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Expression of disease\u2010related mi<scp>RNA<\/scp>s in white\u2010matter lesions of progressive multiple sclerosis brains"],"prefix":"10.1002","volume":"6","author":[{"given":"Ajai","family":"Tripathi","sequence":"first","affiliation":[{"name":"Department of Neurosciences Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Volsko","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ushasi","family":"Datta","sequence":"additional","affiliation":[{"name":"Department of Neurosciences 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