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Correlation of Brain Atrophy, Disability, and Spinal Cord Atrophy in a Murine Model of Multiple Sclerosis
Author(s) -
Paz Soldán M. Mateo,
Raman Mekala R.,
Gamez Jeffrey D.,
Lohrey Anne K.,
Chen Yi,
Pirko Istvan,
Johnson Aaron J.
Publication year - 2015
Publication title -
journal of neuroimaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.822
H-Index - 64
eISSN - 1552-6569
pISSN - 1051-2284
DOI - 10.1111/jon.12250
Subject(s) - atrophy , medicine , multiple sclerosis , spinal cord , pathology , magnetic resonance imaging , brain size , central nervous system , central nervous system disease , radiology , immunology , psychiatry
BACKGROUND Disability progression in multiple sclerosis (MS) remains incompletely understood. Unlike lesional measures, central nervous system atrophy has a strong correlation with disability. Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability. METHODS Infected and control mice were followed for 12 months. Disability was assessed periodically using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4‐5 spinal cord cross‐sectional area measurements were performed using Analyze 10. RESULTS At 3 months, brain atrophy reached statistical significance ( P = .005). In contrast, disability did not differ until 4 months post‐infection ( P = .0005). Cord atrophy reached significance by 9 months ( P = 0.009). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume ( P = .00003), while spinal cord cross‐sectional area was 25.6% reduced ( P = .001) among cases. CONCLUSIONS Our results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate.