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Updated: Apr 14, 2026
Measuring Progressive Neurological Disability in a Mouse Model of Multiple Sclerosis
Published on: November 14, 2016
Correlation of Brain Atrophy, Disability, and Spinal Cord Atrophy in a Murine Model of Multiple Sclerosis
M Mateo Paz Soldán1, Mekala R Raman1, Jeffrey D Gamez1
1Department of Neurology, Mayo Clinic, Rochester, Minnesota.
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.
Insights
Brain atrophy significantly precedes and predicts disability in a multiple sclerosis mouse model. Spinal cord atrophy occurs later, correlating with severe disability, offering insights into disease progression mechanisms.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Multiple sclerosis (MS) disability progression is not fully understood.
- Central nervous system atrophy correlates strongly with disability, unlike lesional measures.
- Theiler's murine encephalomyelitis virus infection in SJL/J mice serves as a progressive MS model.
Purpose of the Study:
- To quantify brain and spinal cord atrophy using in vivo MRI in a mouse model of progressive multiple sclerosis.
- To analyze the temporal relationship between central nervous system atrophy and disability progression.
Main Methods:
- Longitudinal in vivo MRI (7 Tesla) was used to measure brain and spinal cord volumes in infected and control mice over 12 months.
- Disability was assessed using the rotarod assay.
- Volumetric analysis included ventricular volume and spinal cord cross-sectional area.
Main Results:
- Significant brain atrophy was observed by 3 months post-infection, preceding significant disability onset at 4 months.
- Spinal cord atrophy became significant by 9 months.
- By 12 months, infected mice showed increased ventricular volume (111.8%) and reduced spinal cord cross-sectional area (25.6%) compared to controls.
Conclusions:
- Significant brain atrophy precedes and predicts disability development in this MS model.
- Spinal cord atrophy occurs late and correlates with severe disability.
- The temporal relationship provides a framework for understanding disability progression mechanisms in MS.
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