Related Experiment Video
Updated: May 5, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
4D marmoset brain map reveals MRI and molecular signatures for onset of multiple sclerosis-like lesions
Jing-Ping Lin1, Alexis Brake1, Maxime Donadieu1
1Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, Bethesda, MD, USA.
Abstract:
Inferring cellular and molecular dynamics of multiple sclerosis (MS) lesions from postmortem tissue collected decades after onset is challenging. Using magnetic resonance image (MRI)-guided spatiotemporal RNA profiling in marmoset experimental autoimmune encephalitis (EAE), we mapped lesion dynamics and modeled molecular perturbations relevant to MS. Five distinct lesion microenvironments emerged, involving neuroglial responses, tissue destruction and repair, and brain border regulation. Before demyelination, MRI identified a high ratio of proton density-weighted signal to T1 relaxation time, capturing early hypercellularity, and elevated astrocytic and ependymal senescence signals marked perivascular and periventricular areas that later became demyelination hotspots. As lesions expanded, concentric glial barriers formed, initially dominated by proliferating and diversifying microglia and oligodendrocyte precursors, later replaced by monocytes and lymphocytes. We highlight SERPINE1+ astrocytes as a signaling hub underlying lesion onset in both marmoset EAE and MS.
Insights
This study maps multiple sclerosis (MS) lesion dynamics using MRI-guided RNA profiling in EAE. It reveals distinct microenvironments and identifies SERPINE1+ astrocytes as key in lesion onset.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Understanding multiple sclerosis (MS) lesion development from postmortem tissue is difficult.
- Experimental autoimmune encephalitis (EAE) in marmosets offers a model to study MS lesion dynamics.
Purpose of the Study:
- To map the cellular and molecular dynamics of MS lesions using MRI-guided spatiotemporal RNA profiling.
- To model molecular perturbations relevant to MS pathogenesis.
Main Methods:
- Magnetic resonance imaging (MRI)-guided spatiotemporal RNA profiling in marmoset EAE models.
- Analysis of lesion microenvironments, cellular composition, and molecular signaling.
Main Results:
- Identified five distinct lesion microenvironments: neuroglial responses, tissue destruction/repair, and brain border regulation.
- Early MRI signals (high proton density/T1 ratio, astrocytic/ependymal senescence) predicted later demyelination hotspots.
- Lesion expansion involved dynamic glial barriers with sequential infiltration of microglia, oligodendrocyte precursors, monocytes, and lymphocytes.
- SERPINE1+ astrocytes were highlighted as a critical signaling hub at lesion onset.
Conclusions:
- MRI-guided RNA profiling provides insights into MS lesion progression.
- Distinct cellular and molecular changes characterize different stages and locations of MS lesions.
- SERPINE1+ astrocytes play a crucial role in initiating MS lesions.
Related Concept Videos
01:05Atomic Nuclei: Magnetic Resonance
01:24Magnetic Resonance Imaging
01:14Brain Imaging
These technologies include computerized axial tomography (CAT or CT scans), positron-emission tomography (PET scans), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and Transcranial Magnetic...
01:27Imaging Studies IV: Magnetic Resonance Imaging