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Cited by 137Multiple Sclerosis Research StudiesBarrier Structure and Function StudiesCerebrovascular and genetic disorders

Persistent endothelial abnormalities and blood–brain barrier leak in primary and secondary progressive multiple sclerosis

Leech, S., Kirk, J., Plumb, J., McQuaid, S.·2007·Neuropathology and Applied Neurobiology
DOI 10.1111/j.1365-2990.2006.00781.x
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Abstract

Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum protein leak, in tight junctions of the blood–brain barrier endothelium, in lesional and normal‐appearing white matter (NAWM) in secondary progressive (SP) and acute multiple sclerosis (MS). This work is extended here to lesions and NAWM in primary progressive multiple sclerosis (PPMS) and to cortical grey matter in PPMS and SPMS. Immunocytochemistry and semiquantitative confocal microscopy for the tight junction protein zonula occludens 1 (ZO‐1) was performed on snap‐frozen sections from PPMS (n = 6) and controls (n = 5). Data on 2103 blood vessels were acquired from active lesions (n = 10), inactive lesions (n = 15), NAWM (n = 42) and controls (n = 20). Data on 1218 vessels were acquired from normal‐appearing grey matter (PPMS, 5; SPMS, 6; controls, 5). In PPMS abnormal ZO‐1 expression in active white matter lesions and NAWM, was found in 42% and 13% of blood vessels, respectively, comparable to previous data from acute and SPMS. In chronic white matter plaques, however, abnormalities were considerably more frequent (37%) in PPMS than in SPMS. Abnormality was also more frequent in normal‐appearing grey matter in SPMS (23%) than in PPMS (10%). In summary, abnormal tight junctions in both SPMS and PPMS are most frequent in active white matter lesions but persist in inactive lesions, particularly in PPMS. Abnormal tight junctions are also common in normal‐appearing grey matter in SPMS. Persistent endothelial abnormality with leak (PEAL) is therefore widespread but variably expressed in MS and may contribute to disease progression.

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Crossref · 10.1111/j.1365-2990.2006.00781.x

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  • These abnormalities are seen across the brain in both relapsing-remitting and progressive stages of multiple sclerosis, being most common in active lesions.

    “These abnormalities are seen across the brain in both relapsing-remitting and progressive stages of MS (352) being most common in active lesions.”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [352]

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Authors
Leech, S., Kirk, J., Plumb, J., & McQuaid, S.
Affiliations
Queen's University Belfast (GB)
Corresponding author
McQuaid, S.
ORCID
Venue
Neuropathology and Applied Neurobiology
Publisher
Wiley
Published
2007-01-12
Volume
33
Issue
1
Pages
86-98
ISSN
  • 0305-1846 (ISSN-L)
  • 1365-2990
DOI
10.1111/j.1365-2990.2006.00781.x
OpenAlex
W1967616873
Cited by
137
References
4
Citations by year
2026: 4 · 2025: 7 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 9 · 2017: 12 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 10 · 2012: 10
FWCI
6.12
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Neuropathology and Applied Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (submittedVersion)
  • Research Portal (Queen's University Belfast) (submittedVersion)
Funders
  • Wellcome Trust (069411)
  • Multiple Sclerosis Society
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
Keywords
primary progressive multiple sclerosis, secondary progressive multiple sclerosis, endothelial tight junctions, zonula occludens-1, normal-appearing white matter, normal-appearing gray matter, white matter lesions, disease progression
MeSH terms
Adult, Aged, Aged, 80 and over, Axons, Blood-Brain Barrier, Cerebral Cortex, Endothelium, Female, Fluorescent Antibody Technique, Humans, Immunoenzyme Techniques, Male, Middle Aged, Neuroglia, Microscopy, Confocal, Tight Junctions, Multiple Sclerosis, Chronic Progressive

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