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Updated: Jun 30, 2025

An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
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Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology

Petra Kukanja1, Christoffer M Langseth2, Leslie A Rubio Rodríguez-Kirby1

  • 1Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Biomedicum, Karolinska Institutet, 17177 Stockholm, Sweden.

Cell
|March 21, 2024
PubMed

Insights

This study reveals how cellular processes evolve in multiple sclerosis (MS) by mapping disease progression in mice and humans. Researchers identified dynamic glial cell changes and lesion development, offering new insights into MS neuropathology.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Multiple sclerosis (MS) is a chronic neurological disease marked by lesions and ongoing inflammation.
  • While single-cell studies have illuminated MS pathology, the dynamic cellular changes over time are not fully understood.

Purpose of the Study:

  • To investigate the temporal and spatial cellular dynamics of multiple sclerosis (MS) using mouse models and human samples.
  • To understand the evolution of lesions and the role of glial cells in MS pathogenesis.

Main Methods:

  • Single-cell spatial expression profiling using in situ sequencing (ISS) in mouse experimental autoimmune encephalomyelitis (EAE) models.
  • Spatial mapping of archival human MS spinal cord tissue.
  • Modeling temporal and regional disease progression rates.

Main Results:

  • Active MS lesions evolve centrifugally, with disease-associated (DA)-glia arising independently and dynamically throughout the disease course.
  • Spatial mapping in human MS tissues confirmed distinct glial distributions and allowed deconvolution of active/inactive lesions into sub-compartments.
  • New lesion areas were identified in human MS spinal cords.

Conclusions:

  • This research establishes a high-resolution spatial resource for MS neuropathology in both mouse and human tissues.
  • The study elucidates the intricate, dynamic cellular processes underlying MS lesion development and progression.
  • Findings provide a deeper understanding of glial cell involvement and lesion heterogeneity in multiple sclerosis.
Keywords:
EAEMSSERPINA3Serpina3ndisease-associated gliaexperimental autoimmune encephalomyelitisin situ sequencingmultiple sclerosisneuroinflammationneuropathologysingle-cellspatial sequencing

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