{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:07:36Z","timestamp":1787062056640,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research","award":["167270"],"award-info":[{"award-number":["167270"]}]},{"name":"Canadian Institutes of Health Research","award":["W81XWH2210468"],"award-info":[{"award-number":["W81XWH2210468"]}]},{"name":"USA Department of Defense Multiple Sclerosis Research Program","award":["167270"],"award-info":[{"award-number":["167270"]}]},{"name":"USA Department of Defense Multiple Sclerosis Research Program","award":["W81XWH2210468"],"award-info":[{"award-number":["W81XWH2210468"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The extracellular matrix (ECM) of the central nervous system (CNS) is an interconnected network of proteins and sugars with critical roles in both homeostasis and disease. In neurological diseases, excessive ECM deposition and remodeling impact both injury and repair. CNS lesions of multiple sclerosis (MS), a chronic inflammatory and degenerative disease, cause prominent alterations of the ECM. However, there are a lack of data investigating how the multitude of ECM members change in relation to each other and how this affects the MS disease course. Here, we evaluated ECM changes in MS lesions compared to a control brain using databases generated in-house through spatial mRNA-sequencing and through a public resource of single-nucleus RNA sequencing previously published by Absinta and colleagues. These results underline the importance of publicly available datasets to find new targets of interest, such as the ECM. Both spatial and public datasets demonstrated widespread changes in ECM molecules and their interacting proteins, including alterations to proteoglycans and glycoproteins within MS lesions. Some of the altered ECM members have been described in MS, but other highly upregulated members, including the SPARC family of proteins, have not previously been highlighted. SPARC family members are upregulated in other conditions by reactive astrocytes and may influence immune cell activation and MS disease course. The profound changes to the ECM in MS lesions deserve more scrutiny as they impact neuroinflammation, injury, and repair.<\/jats:p>","DOI":"10.3390\/ijms25021240","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T07:00:32Z","timestamp":1705647632000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Uncovering Novel Extracellular Matrix Transcriptome Alterations in Lesions of Multiple Sclerosis"],"prefix":"10.3390","volume":"25","author":[{"given":"Erin Laurel","family":"Stephenson","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB T2N 2T9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv William","family":"Jain","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Ghorbani","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianne Petra","family":"Gorter","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"D\u2019Mello","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2600-3563","authenticated-orcid":false,"given":"Voon Wee","family":"Yong","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrn3550","article-title":"Pathophysiology of the brain extracellular matrix: A new target for remyelination","volume":"14","author":"Lau","year":"2013","journal-title":"Nat. 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