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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...

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Published: Swansea 2026
Institution: Swansea University
Degree level: Master of Research
Degree name: MRes
Supervisor: Howell, Owain W.
URI: https://cronfa.swan.ac.uk/Record/cronfa72112
first_indexed 2026-06-18T13:47:48Z
last_indexed 2026-06-19T05:50:48Z
id cronfa72112
recordtype RisThesis
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spelling 2026-06-18T16:51:37.7721764 v2 72112 2026-06-18 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 4786383f75c2063a66625ba8fc504769 JEAN OLIVEIRA JEAN OLIVEIRA true false 2026-06-18 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. E-Thesis Swansea Macrophage, Microglia, Multiple Sclerosis, Neuroinflammation 11 6 2026 2026-06-11 ORCiD identifier: https://orcid.org/0009-0006-4908-2360 COLLEGE NANME COLLEGE CODE Swansea University Howell, Owain W. Master of Research MRes 2026-06-18T16:51:37.7721764 2026-06-18T14:42:52.6044140 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science JEAN OLIVEIRA 1
title 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
spellingShingle 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
author_id_str_mv 4786383f75c2063a66625ba8fc504769
author_id_fullname_str_mv 4786383f75c2063a66625ba8fc504769_***_JEAN OLIVEIRA
author JEAN OLIVEIRA
author2 JEAN OLIVEIRA
format E-Thesis
publishDate 2026
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
document_store_str 0
active_str 0
description 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.
published_date 2026-06-11T06:03:10Z
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score 11.109323

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