Researchers have investigated the composition and communication of cells in subcortical lesions – tissue damage to deep brain structures at different stages of multiple sclerosis. Their investigation has provided new insights into the molecular mechanisms that influence the progression of this chronic disease. 

MS is an inflammatory, progressive disease of the central nervous system in which the immune system attacks nerve tissue and causes permanent damage. Multiple lesions form in different regions of the nervous system, which are initially inflammatory and then evolve over time into chronic, noninflammatory forms. A so-called chronic-active intermediate stage is characteristic, in which the lesions are surrounded by an inflamed rim, where iron deposits are often found, indicating a lack of repair mechanisms.

To more precisely map the cells and signaling pathways in these areas of tissue damage, an international team of researchers, led by the Mannheim and Heidelberg Medical Faculties of Heidelberg University, Germany, used state-of-the-art spatial and single-cell nuclear transcriptome techniques, accompanied by complex bioinformatic analyses. This enabled them to localize and analyze cell types and their signaling pathways in subcortical MS tissue and control tissue.

The researchers were able to examine at high resolution areas of tissue, such as around blood vessels, that are linked to immune cell migration. They also focused on the inflamed rim and center of lesions, where they identified a specific type of astrocyte that carries cilia but has not yet been characterized in detail.

A special focus was on the inflamed edge of chronically active lesions, where the team studied interactions between myeloid, endothelial, and glial cell types. These interactions contribute to the development and progression of the lesions and provide clues as to how communication processes between the cells might be specifically influenced.

The researchers said a deeper understanding of these interactions will help to develop targeted therapies that are adapted to specific cell types and their communication in specific tissue niches. The development and application of complex bioinformatics scripts was crucial in order to integrate and analyze the large transcriptome data sets.

The findings were published in the journal Nature Neuroscience.