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Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis

Roberta Magliozzi Orcid Logo, Owain Howell Orcid Logo, Massimiliano Calabrese Orcid Logo, Richard Reynolds Orcid Logo

Nature Reviews Neurology, Volume: 19, Issue: 8, Pages: 461 - 476

Swansea University Author: Owain Howell Orcid Logo

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DOI (Published version): 10.1038/s41582-023-00838-7

Abstract

Growing evidence from cerebrospinal fluid samples and post-mortem brain tissue from individuals with multiple sclerosis (MS) and rodent models indicates that the meninges have a key role in the inflammatory and neurodegenerative mechanisms underlying progressive MS pathology. The subarachnoid space...

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Published in: Nature Reviews Neurology
ISSN: 1759-4758 1759-4766
Published: Springer Science and Business Media LLC 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa63789
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spelling v2 63789 2023-07-06 Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false 2023-07-06 BMS Growing evidence from cerebrospinal fluid samples and post-mortem brain tissue from individuals with multiple sclerosis (MS) and rodent models indicates that the meninges have a key role in the inflammatory and neurodegenerative mechanisms underlying progressive MS pathology. The subarachnoid space and associated perivascular spaces between the membranes of the meninges are the access points for entry of lymphocytes, monocytes and macrophages into the brain parenchyma, and the main route for diffusion of inflammatory and cytotoxic molecules from the cerebrospinal fluid into the brain tissue. In addition, the meningeal spaces act as an exit route for CNS-derived antigens, immune cells and metabolites. A number of studies have demonstrated an association between chronic meningeal inflammation and a more severe clinical course of MS, suggesting that the build-up of immune cell aggregates in the meninges represents a rational target for therapeutic intervention. Therefore, understanding the precise cell and molecular mechanisms, timing and anatomical features involved in the compartmentalization of inflammation within the meningeal spaces in MS is vital. Here, we present a detailed review and discussion of the cellular, molecular and radiological evidence for a role of meningeal inflammation in MS, alongside the clinical and therapeutic implications. Journal Article Nature Reviews Neurology 19 8 461 476 Springer Science and Business Media LLC 1759-4758 1759-4766 Multiple Sclerosis, Neuroimmunology. 1 8 2023 2023-08-01 10.1038/s41582-023-00838-7 http://dx.doi.org/10.1038/s41582-023-00838-7 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2023-09-05T15:21:56.6442426 2023-07-06T13:33:48.2675777 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Roberta Magliozzi 0000-0001-8284-7763 1 Owain Howell 0000-0003-2157-9157 2 Massimiliano Calabrese 0000-0002-3362-7403 3 Richard Reynolds 0000-0003-4622-4694 4 Under embargo Under embargo 2023-09-05T15:16:42.5851034 Output 2866175 application/pdf Accepted Manuscript true 2024-01-03T00:00:00.0000000 true eng
title Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis
spellingShingle Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis
Owain Howell
title_short Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis
title_full Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis
title_fullStr Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis
title_full_unstemmed Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis
title_sort Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis
author_id_str_mv 58c995486fc93a242b987640b692db8c
author_id_fullname_str_mv 58c995486fc93a242b987640b692db8c_***_Owain Howell
author Owain Howell
author2 Roberta Magliozzi
Owain Howell
Massimiliano Calabrese
Richard Reynolds
format Journal article
container_title Nature Reviews Neurology
container_volume 19
container_issue 8
container_start_page 461
publishDate 2023
institution Swansea University
issn 1759-4758
1759-4766
doi_str_mv 10.1038/s41582-023-00838-7
publisher Springer Science and Business Media LLC
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
url http://dx.doi.org/10.1038/s41582-023-00838-7
document_store_str 0
active_str 0
description Growing evidence from cerebrospinal fluid samples and post-mortem brain tissue from individuals with multiple sclerosis (MS) and rodent models indicates that the meninges have a key role in the inflammatory and neurodegenerative mechanisms underlying progressive MS pathology. The subarachnoid space and associated perivascular spaces between the membranes of the meninges are the access points for entry of lymphocytes, monocytes and macrophages into the brain parenchyma, and the main route for diffusion of inflammatory and cytotoxic molecules from the cerebrospinal fluid into the brain tissue. In addition, the meningeal spaces act as an exit route for CNS-derived antigens, immune cells and metabolites. A number of studies have demonstrated an association between chronic meningeal inflammation and a more severe clinical course of MS, suggesting that the build-up of immune cell aggregates in the meninges represents a rational target for therapeutic intervention. Therefore, understanding the precise cell and molecular mechanisms, timing and anatomical features involved in the compartmentalization of inflammation within the meningeal spaces in MS is vital. Here, we present a detailed review and discussion of the cellular, molecular and radiological evidence for a role of meningeal inflammation in MS, alongside the clinical and therapeutic implications.
published_date 2023-08-01T15:21:58Z
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