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Updated: Sep 21, 2026
Bioluminescence and Near-infrared Imaging of Optic Neuritis and Brain Inflammation in the EAE Model of Multiple Sclerosis in Mice
Published on: March 1, 2017
MRI-based monitoring of inflammation and tissue damage in acute and chronic relapsing EAE
M Rausch1, P Hiestand, D Baumann
1Novartis Institute for Biomedical Research, Basel, Switzerland. martin.rausch@pharma.novartis.com
Abstract:
Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model that in several respects mimics human multiple sclerosis (MS), and can be used to design or validate new strategies for treatment of this disease. In the present study, different MRI techniques (macrophage tracking based on labeling cells in vivo by ultrasmall particles of iron oxide (USPIO), blood-brain barrier (BBB) breakdown, and magnetization transfer imaging (MTI)), as well as immunohistological staining were used to study the burden of disease in Lewis rats immunized by guinea pig myelin. The resulting imaging data was compared with behavioral readouts. Animals were studied during the acute phase and the first relapse. Activated monocytes were detected during both episodes in the brain stem or cortex. These areas coincided in part with areas of BBB breakdown. Significant changes of the magnetization transfer ratios (MTRs) of up to 35% were observed in areas of USPIO accumulation. This suggests that infiltrating monocytes are the major source of demyelination in EAE, but monocyte infiltration and breakdown of the BBB are temporally or spatially independent inflammatory processes.
Insights
Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), reveals infiltrating monocytes drive demyelination. Monocyte infiltration and blood-brain barrier (BBB) breakdown appear as independent inflammatory processes.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Magnetic Resonance Imaging (MRI)
Background:
- Experimental autoimmune encephalomyelitis (EAE) serves as a key animal model for human multiple sclerosis (MS).
- Understanding the dynamics of neuroinflammation and demyelination in EAE is crucial for developing effective MS therapies.
Purpose of the Study:
- To investigate the role of infiltrating monocytes in demyelination during EAE using advanced MRI techniques.
- To compare imaging findings with behavioral outcomes in EAE rats during acute and relapsing phases.
Main Methods:
- Utilized in vivo ultrasmall particles of iron oxide (USPIO) for macrophage tracking.
- Employed blood-brain barrier (BBB) breakdown assessment and magnetization transfer imaging (MTI).
- Correlated MRI data with immunohistological staining and behavioral readouts in Lewis rats.
Main Results:
- Activated monocytes were detected in the brain stem and cortex during acute and relapsing EAE phases.
- Areas of USPIO accumulation showed significant magnetization transfer ratio (MTR) changes (up to 35%), indicating demyelination.
- Monocyte infiltration partially overlapped with BBB breakdown sites, but these processes were temporally and spatially independent.
Conclusions:
- Infiltrating monocytes are identified as the primary drivers of demyelination in the EAE model.
- The findings suggest that monocyte infiltration and BBB breakdown are distinct inflammatory events in EAE pathogenesis.
- This study highlights the utility of combined MRI techniques for dissecting inflammatory processes in neurodegenerative diseases like MS.
