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Updated: Oct 5, 2025
Isolating Central Nervous System Tissues and Associated Meninges for the Downstream Analysis of Immune cells
Published on: May 19, 2020
Accumulation of meningeal lymphocytes correlates with white matter lesion activity in progressive multiple sclerosis
Shanzeh M Ahmed1, Nina L Fransen2,3, Hanane Touil4
1Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Abstract:
Subpial cortical demyelination is an important component of multiple sclerosis (MS) pathology contributing to disease progression, yet mechanism(s) underlying its development remain unclear. Compartmentalized inflammation involving the meninges may drive this type of injury. Given recent findings identifying substantial white matter (WM) lesion activity in patients with progressive MS, elucidating whether and how WM lesional activity relates to meningeal inflammation and subpial cortical injury is of interest. Using postmortem FFPE tissue blocks (range, 5-72 blocks; median, 30 blocks) for each of 27 patients with progressive MS, we assessed the relationship between meningeal inflammation, the extent of subpial cortical demyelination, and the state of subcortical WM lesional activity. Meningeal accumulations of T cells and B cells, but not myeloid cells, were spatially adjacent to subpial cortical lesions, and greater immune cell accumulation was associated with larger subpial lesion areas. Patients with a higher extent of meningeal inflammation harbored a greater proportion of active and mixed active/inactive WM lesions and an overall lower proportion of inactive and remyelinated WM lesions. Our findings support the involvement of meningeal lymphocytes in subpial cortical injury and point to a potential link between inflammatory subpial cortical demyelination and pathological mechanisms occurring in the subcortical WM.
Insights
Meningeal inflammation, particularly T and B cells, is linked to subpial cortical demyelination in multiple sclerosis (MS). This inflammation also correlates with active white matter lesions, suggesting a connection between meningeal and white matter pathology in progressive MS.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Subpial cortical demyelination is a key feature of multiple sclerosis (MS) pathology, contributing to disease progression.
- The mechanisms driving subpial cortical demyelination are not fully understood, but meningeal inflammation is a potential contributor.
- Understanding the relationship between meningeal inflammation, cortical injury, and white matter (WM) lesion activity is crucial for progressive MS.
Purpose of the Study:
- To investigate the association between meningeal inflammation, subpial cortical demyelination, and white matter (WM) lesion activity in progressive multiple sclerosis (MS).
- To determine the types of immune cells involved in meningeal inflammation adjacent to cortical lesions.
- To explore the link between the extent of meningeal inflammation and the activity status of WM lesions.
Main Methods:
- Analysis of postmortem FFPE tissue blocks from 27 patients with progressive MS.
- Assessment of meningeal inflammation, subpial cortical demyelination, and subcortical WM lesion activity.
- Quantification of T cells, B cells, and myeloid cells in meningeal accumulations.
Main Results:
- Meningeal accumulations of T cells and B cells, but not myeloid cells, were spatially associated with subpial cortical lesions.
- Greater immune cell accumulation in the meninges correlated with larger subpial lesion areas.
- Higher levels of meningeal inflammation were linked to a greater proportion of active WM lesions and fewer inactive/remyelinated lesions.
Conclusions:
- Meningeal lymphocytes play a role in driving subpial cortical injury in progressive MS.
- A potential link exists between inflammatory subpial cortical demyelination and pathological processes in the subcortical white matter.
- These findings highlight the importance of the meninges in MS pathogenesis and suggest therapeutic targets for cortical and white matter lesions.
