Extensive extracellular matrix depositions in active multiple sclerosis lesions.
Open accessAbstract
In the central nervous system, basement membrane (BM) constituents are predominantly associated with the vasculature. However, under inflammatory conditions, the expression of BM components may alter. Here, we investigated the distribution of several BM components, including laminin, collagen type IV and heparan sulfate proteoglycans in various multiple sclerosis (MS) lesions. We observed irregular and discontinuous BMs in active lesions. Throughout active MS lesions, we found dense networks of BM proteins, which were surprisingly not associated with the cerebrovasculature. These striking parenchymal networks were not observed in chronic inactive MS lesions and brains of non-neurological controls. In addition, we studied the distribution of transforming growth factor-beta1 (TGF-beta1), since it is known as a major modulator of ECM production. Leukocytes, in particular CD68-positive macrophages, expressed high levels of TGF-beta1 and were located in close proximity to parenchymal BM deposits in the MS lesions. We postulate that these BM networks may play a role in the further recruitment of inflammatory cells and form a barrier for axonal regeneration.
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Increased number of PDGFRβ-expressing cells are detected in human MS pathology samples and increased ECM protein deposition is a common pathological feature of MS lesions.
“Increased number of PDGFRβ-expressing cells are detected in human MS pathology samples”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as van Horssen et al., 2006
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“…are detected in human MS pathology samples (Dias et al., 2020) and increased ECM protein deposition is a common pathological feature of MS lesions (van Horssen et al., 2006), further supporting fibroblast driven fibrosis as a feature of MS. Continued studies on the mechanisms and consequences of…”
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- Authors
- van Horssen, J., Bö, L., Dijkstra, C. D., & de Vries, H. E.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 24
- Issue
- 3
- Pages
- 484-491
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2037725018
- Cited by
- 119
- References
- 37
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 8 · 2023: 9 · 2022: 3 · 2021: 12 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 8 · 2016: 4 · 2015: 11 · 2014: 4 · 2013: 9 · 2012: 5
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- multiple sclerosis, extracellular matrix, basement membrane, laminin, type IV collagen, heparan sulfate proteoglycans, TGF-β1, macrophages, CD68, active lesions, axon regeneration, inflammatory cell recruitment, neuroinflammation
- MeSH terms
- Adult, Aged, Basement Membrane, Brain, Female, Humans, Immunohistochemistry, Laminin, Leukocytes, Male, Middle Aged, Multiple Sclerosis, Nerve Degeneration, Reference Values, Tissue Distribution, Trehalase, Transforming Growth Factor beta, Heparan Sulfate Proteoglycans, Collagen Type IV, Saccharomyces cerevisiae Proteins
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