Pilot functional magnetic resonance imaging study of clemastine‐aided functional recovery on a mouse model of demyelination
ABSTRACT Background 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 f...
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Wiley
2025-03-01
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| Series: | Neuroprotection |
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| Online Access: | https://doi.org/10.1002/nep3.70 |
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| author | Ander Egimendia Irati L. de laPisa Daniel Padro Lorena Colás Sandra Plaza‐García David Otaegui Pedro Ramos‐Cabrer |
| author_facet | Ander Egimendia Irati L. de laPisa Daniel Padro Lorena Colás Sandra Plaza‐García David Otaegui Pedro Ramos‐Cabrer |
| author_sort | Ander Egimendia |
| collection | DOAJ |
| description | ABSTRACT Background 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‐state functional magnetic resonance imaging in a cuprizone murine model of demyelination to investigate these unsolved questions. Methods Three groups of (n = 6) 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‐week period to compare controls vs spontaneous (cuprizone group) vs clemastine‐aided (clemastine group) remyelination group. Group clemastine was treated with this antihistaminic (oral gavage) during the remyelination period (Weeks 5–10). Anatomical magnetic resonance imaging (T2w‐MRI) and resting state functional MRI (rs‐FMRI) 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‐free functional imaging and seed‐based correlation. This study uses the t‐test and the D'Agostino–Pearson normality test to make an assessment. Results The principal findings of our research include: (1) cuprizone‐treated 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‐aided remyelination re‐establishes normal thalamocortical connectivity at 6 months after demyelination. Conclusion This approach provides insights into the dynamic processes of demyelination and remyelination, informing the development of more effective interventions for MS. |
| format | Article |
| id | doaj-art-2eaf4e22155743e1b658cff34d904cde |
| institution | DOAJ |
| issn | 2770-7296 2770-730X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Neuroprotection |
| spelling | doaj-art-2eaf4e22155743e1b658cff34d904cde2025-08-20T02:40:29ZengWileyNeuroprotection2770-72962770-730X2025-03-013110411510.1002/nep3.70Pilot functional magnetic resonance imaging study of clemastine‐aided functional recovery on a mouse model of demyelinationAnder Egimendia0Irati L. de laPisa1Daniel Padro2Lorena Colás3Sandra Plaza‐García4David Otaegui5Pedro Ramos‐Cabrer6Center for Cooperative Research in Biomaterials (CIC BiomaGUNE) Basque Research and Technology Alliance (BRTA) San Sebastian SpainCenter for Cooperative Research in Biomaterials (CIC BiomaGUNE) Basque Research and Technology Alliance (BRTA) San Sebastian SpainCenter for Cooperative Research in Biomaterials (CIC BiomaGUNE) Basque Research and Technology Alliance (BRTA) San Sebastian SpainCenter for Cooperative Research in Biomaterials (CIC BiomaGUNE) Basque Research and Technology Alliance (BRTA) San Sebastian SpainCenter for Cooperative Research in Biomaterials (CIC BiomaGUNE) Basque Research and Technology Alliance (BRTA) San Sebastian SpainNeuroimmunology Group, Neuroscience Area Biogipuzkoa Health Research Institute San Sebastian SpainCenter for Cooperative Research in Biomaterials (CIC BiomaGUNE) Basque Research and Technology Alliance (BRTA) San Sebastian SpainABSTRACT Background 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‐state functional magnetic resonance imaging in a cuprizone murine model of demyelination to investigate these unsolved questions. Methods Three groups of (n = 6) 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‐week period to compare controls vs spontaneous (cuprizone group) vs clemastine‐aided (clemastine group) remyelination group. Group clemastine was treated with this antihistaminic (oral gavage) during the remyelination period (Weeks 5–10). Anatomical magnetic resonance imaging (T2w‐MRI) and resting state functional MRI (rs‐FMRI) 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‐free functional imaging and seed‐based correlation. This study uses the t‐test and the D'Agostino–Pearson normality test to make an assessment. Results The principal findings of our research include: (1) cuprizone‐treated 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‐aided remyelination re‐establishes normal thalamocortical connectivity at 6 months after demyelination. Conclusion This approach provides insights into the dynamic processes of demyelination and remyelination, informing the development of more effective interventions for MS.https://doi.org/10.1002/nep3.70clemastinecuprizonedemyelinationmagnetic resonance imagingremyelination |
| spellingShingle | Ander Egimendia Irati L. de laPisa Daniel Padro Lorena Colás Sandra Plaza‐García David Otaegui Pedro Ramos‐Cabrer Pilot functional magnetic resonance imaging study of clemastine‐aided functional recovery on a mouse model of demyelination Neuroprotection clemastine cuprizone demyelination magnetic resonance imaging remyelination |
| title | Pilot functional magnetic resonance imaging study of clemastine‐aided functional recovery on a mouse model of demyelination |
| title_full | Pilot functional magnetic resonance imaging study of clemastine‐aided functional recovery on a mouse model of demyelination |
| title_fullStr | Pilot functional magnetic resonance imaging study of clemastine‐aided functional recovery on a mouse model of demyelination |
| title_full_unstemmed | Pilot functional magnetic resonance imaging study of clemastine‐aided functional recovery on a mouse model of demyelination |
| title_short | Pilot functional magnetic resonance imaging study of clemastine‐aided functional recovery on a mouse model of demyelination |
| title_sort | pilot functional magnetic resonance imaging study of clemastine aided functional recovery on a mouse model of demyelination |
| topic | clemastine cuprizone demyelination magnetic resonance imaging remyelination |
| url | https://doi.org/10.1002/nep3.70 |
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