E-Thesis 12 views
The role of the diffuse microglia and macrophage activation in the non-lesion brain tissue in multiple sclerosis progression: a retrospective post-mortem cohort study / JEAN OLIVEIRA
Swansea University Author: JEAN OLIVEIRA
Abstract
Introduction: Diffuse microglial/macrophage activation (DMA) in non-lesion tissue is a neuropathological feature of multiple sclerosis (MS) pathology, associated with progression. However, the role of DMA in initiating, sustaining, or driving progression is unknown. We investigated the extent and co...
| Published: |
Swansea
2026
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| Institution: | Swansea University |
| Degree level: | Master of Research |
| Degree name: | MRes |
| Supervisor: | Howell, Owain W. |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa72112 |
| Abstract: |
Introduction: Diffuse microglial/macrophage activation (DMA) in non-lesion tissue is a neuropathological feature of multiple sclerosis (MS) pathology, associated with progression. However, the role of DMA in initiating, sustaining, or driving progression is unknown. We investigated the extent and contribution of DMA to tissue injury and clinical severity in a national post-mortem cohort. Methodology: DMA densities (HLA-D+ pixel percentage) in the normal-appearing thalamus, the superior frontal gyrus white matter (SFG-WM) and grey matter (SFG-GM), and basal pons were determined from 786 tissue sections (n=286 cases), and comparisons to pathological and clinical milestones were made. Results: DMA was highest in the pons (5.3%; approximately two-fold higher than all other brain regions). Non-parametric Spearman's analysis revealed that 1) the extent of DMA strongly correlated between all sampled areas (r=0.50 to 0.94, p<1x10-6), 2) DMA correlated with presence of active lesions and extent of perivascular/meningeal inflammation (r=0.20 to 0.30, p<0.001), 3) there was no association with neuron density or weak with demyelination (r=-0.05 to 0.17), and 4) the pons and thalamus DMA correlated with age of onset (r=-0.16 to -0.21, p<0.001) but not with time to disability milestones or disease duration (r=-0.09 to 0.02). Conclusion: Systematic sampling of a large postmortem cohort demonstrated the ubiquity of DMA in the brain. It provided modest evidence that DMA has subtle contributions to progression-specific pathological processes and with age, but not disease duration. Further microglial populational phenotyping is required to understand the relationship between DMA in progressive MS. |
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| Item Description: |
ORCiD identifier: https://orcid.org/0009-0006-4908-2360 |
| Keywords: |
Macrophage, Microglia, Multiple Sclerosis, Neuroinflammation |
| College: |
Faculty of Medicine, Health and Life Sciences |