{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T04:19:36Z","timestamp":1743567576460,"version":"3.40.3"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD21\/0006\/0016"],"award-info":[{"award-number":["RD21\/0006\/0016"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003989","name":"Ikerbasque, Basque Foundation for Science","doi-asserted-by":"publisher","award":["Ikerbasque Professors Program"],"award-info":[{"award-number":["Ikerbasque Professors Program"]}],"id":[{"id":"10.13039\/501100003989","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuroprotection"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Multiple sclerosis (MS) is a chronic demyelinating disease characterized by autoimmune attacks on myelin sheaths. Its deleterious effects may be reversed by remyelination, a process that restores the integrity of myelin sheaths and, consequently, neuronal function. However, the functional implications of demyelination and remyelination in MS, as well as the potential impact of therapeutic interventions, remain incompletely understood. We used noninvasive longitudinal resting\u2010state functional magnetic resonance imaging in a cuprizone murine model of demyelination to investigate these unsolved questions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three groups of (<jats:italic>n<\/jats:italic>\u2009=\u20096) animals were studied. A control group was fed with standard food for 5 weeks while two treatment groups (cuprizone and clemastine) suffered progressive demyelination by feeding them with 2% cuprizone. At Week 5 (W5), all animals returned to the standard diet and studied for another 5\u2010week period to compare controls vs spontaneous (cuprizone group) vs clemastine\u2010aided (clemastine group) remyelination group. Group clemastine was treated with this antihistaminic (oral gavage) during the remyelination period (Weeks 5\u201310). Anatomical magnetic resonance imaging (T2w\u2010MRI) and resting state functional MRI (rs\u2010FMRI) studies were conducted on weeks W0, W2, W5 (maximal demyelination) W7 and W10 (remyelination). MRI images were processed with the FMRIB Software Library, involving seed\u2010free functional imaging and seed\u2010based correlation. This study uses the <jats:italic>t<\/jats:italic>\u2010test and the D'Agostino\u2013Pearson normality test to make an assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The principal findings of our research include: (1) cuprizone\u2010treated animals suffer an initial phase of elevated connectivity at Week 2 with respect to controls, transitioning to reduced connectivity at Week 5; (2) different temporal trajectories across brain regions, reflecting varying susceptibility to demyelination; (3) while spontaneous remyelination normalizes connectivity in most networks at Week 10 (5 weeks after ceasing cuprizone intoxication), the thalamocortical axis exhibits lasting disruption even 6 months after normalization of diet; and (4) on the contrary, clemastine\u2010aided remyelination re\u2010establishes normal thalamocortical connectivity at 6 months after demyelination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This approach provides insights into the dynamic processes of demyelination and remyelination, informing the development of more effective interventions for MS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nep3.70","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T05:35:44Z","timestamp":1736314544000},"page":"104-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pilot functional magnetic resonance imaging study of clemastine\u2010aided functional recovery on a mouse model of demyelination"],"prefix":"10.1002","volume":"3","author":[{"given":"Ander","family":"Egimendia","sequence":"first","affiliation":[{"name":"Center for Cooperative Research in Biomaterials (CIC BiomaGUNE) Basque Research and Technology Alliance (BRTA) San Sebastian Spain"},{"name":"Neuroimmunology Group, Neuroscience Area Biogipuzkoa Health Research Institute San Sebastian Spain"},{"name":"Neurodegenerative Diseases Research 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