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Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis

Atrophy has become a clinically relevant marker of progressive neurodegeneration in multiple sclerosis (MS). To better understand atrophy, mouse models that feature atrophy along with other aspects of MS are needed. The experimental autoimmune encephalomyelitis (EAE) mouse model of MS was used to de...

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Autores principales: Hamilton, A. Max, Forkert, Nils D., Yang, Runze, Wu, Ying, Rogers, James A., Yong, V. Wee, Dunn, Jeff F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560061/
https://www.ncbi.nlm.nih.gov/pubmed/31186441
http://dx.doi.org/10.1038/s41598-019-44682-6
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author Hamilton, A. Max
Forkert, Nils D.
Yang, Runze
Wu, Ying
Rogers, James A.
Yong, V. Wee
Dunn, Jeff F.
author_facet Hamilton, A. Max
Forkert, Nils D.
Yang, Runze
Wu, Ying
Rogers, James A.
Yong, V. Wee
Dunn, Jeff F.
author_sort Hamilton, A. Max
collection PubMed
description Atrophy has become a clinically relevant marker of progressive neurodegeneration in multiple sclerosis (MS). To better understand atrophy, mouse models that feature atrophy along with other aspects of MS are needed. The experimental autoimmune encephalomyelitis (EAE) mouse model of MS was used to determine the extent of atrophy in a model of inflammation-associated central nervous system pathology. High-resolution magnetic resonance imaging (MRI) and atlas-based volumetric analysis were performed to measure brain regional volumes in EAE mice. EAE brains were larger at peak clinical disease (days 14–16) compared to controls, with affected regions including the cerebellum, hippocampus, and corpus callosum. Following peak clinical disease, EAE mice exhibited significant loss of volume at chronic long-term disease duration (day 66+). Atrophy was identified in both white and grey matter regions including the cerebral cortex, cerebellum, hippocampus, corpus callosum, basal forebrain, midbrain, optic tract, and colliculus. Histological analysis of the atrophied cortex, cerebellum, and hippocampus showed demyelination, and axonal/neuronal loss. We hypothesize this atrophy could be a result of inflammatory associated neurodegenerative processes, which may also be involved in MS. Using MRI and atlas-based volumetrics, EAE has the potential to be a test bed for treatments aimed at reducing progressive neurological deterioration in MS.
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spelling pubmed-65600612019-06-19 Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis Hamilton, A. Max Forkert, Nils D. Yang, Runze Wu, Ying Rogers, James A. Yong, V. Wee Dunn, Jeff F. Sci Rep Article Atrophy has become a clinically relevant marker of progressive neurodegeneration in multiple sclerosis (MS). To better understand atrophy, mouse models that feature atrophy along with other aspects of MS are needed. The experimental autoimmune encephalomyelitis (EAE) mouse model of MS was used to determine the extent of atrophy in a model of inflammation-associated central nervous system pathology. High-resolution magnetic resonance imaging (MRI) and atlas-based volumetric analysis were performed to measure brain regional volumes in EAE mice. EAE brains were larger at peak clinical disease (days 14–16) compared to controls, with affected regions including the cerebellum, hippocampus, and corpus callosum. Following peak clinical disease, EAE mice exhibited significant loss of volume at chronic long-term disease duration (day 66+). Atrophy was identified in both white and grey matter regions including the cerebral cortex, cerebellum, hippocampus, corpus callosum, basal forebrain, midbrain, optic tract, and colliculus. Histological analysis of the atrophied cortex, cerebellum, and hippocampus showed demyelination, and axonal/neuronal loss. We hypothesize this atrophy could be a result of inflammatory associated neurodegenerative processes, which may also be involved in MS. Using MRI and atlas-based volumetrics, EAE has the potential to be a test bed for treatments aimed at reducing progressive neurological deterioration in MS. Nature Publishing Group UK 2019-06-11 /pmc/articles/PMC6560061/ /pubmed/31186441 http://dx.doi.org/10.1038/s41598-019-44682-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hamilton, A. Max
Forkert, Nils D.
Yang, Runze
Wu, Ying
Rogers, James A.
Yong, V. Wee
Dunn, Jeff F.
Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis
title Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis
title_full Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis
title_fullStr Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis
title_full_unstemmed Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis
title_short Central nervous system targeted autoimmunity causes regional atrophy: a 9.4T MRI study of the EAE mouse model of Multiple Sclerosis
title_sort central nervous system targeted autoimmunity causes regional atrophy: a 9.4t mri study of the eae mouse model of multiple sclerosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560061/
https://www.ncbi.nlm.nih.gov/pubmed/31186441
http://dx.doi.org/10.1038/s41598-019-44682-6
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