The blood-brain barrier in cortical multiple sclerosis lesions
Abstract
The blood-brain barrier (BBB) is composed mainly of specialized endothelial cells characterized by the presence of intercellular tight junctions. Additionally, perivascular cells, astrocytes, and surrounding basement membranes determine BBB integrity. BBB disruption is an early phenomenon in the formation of new white matter multiple sclerosis (MS) lesions; however, knowledge of the extent of BBB changes in gray matter MS lesions is lacking. Here, we studied several markers for BBB integrity in well-characterized brain tissue of patients with MS. Plasma protein leakage was enhanced in white matter lesions compared with that in normal-appearing white matter, whereas plasma protein leakage was absent in gray matter lesions. White matter lesions showed irregular basement membranes and parenchymal depositions of collagen type IV, whereas purely gray matter lesions lacked basement membrane alterations. Similarly, we observed no evidence for astrogliosis and tight junction changes in cortical MS lesions. Although BBB dysfunction is a common feature of white matter MS lesions, cortical MS lesions lack markers for BBB disruption or astrogliosis. Our data may indicate that BBB breakdown is not a critical event in the formation of gray matter MS lesions.
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The increased TSPO expression in leukocortical lesions but not other grey matter lesions may reflect the greater microglia and astrocyte activity in the white matter.
“This may well reflect the greater microglia and astrocyte activity in the white matter; pure cortical lesions in post-mortem tissues show little or no inflammation (Bo et al., 2004; Brink et al., 2005; van Horssen et al., 2007), although early lesions have been associated with prominent microglial activation (Lucchinetti et al., 2011).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as van Horssen et al., 2007
Pure cortical lesions in post-mortem tissues show little or no inflammation.
“This may well reflect the greater microglia and astrocyte activity in the white matter; pure cortical lesions in post-mortem tissues show little or no inflammation (Bo et al., 2004; Brink et al., 2005; van Horssen et al., 2007), although early lesions have been associated with prominent microglial activation (Lucchinetti et al., 2011).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as van Horssen et al., 2007
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- Authors
- van Horssen, J., Brink, B. P., de Vries, H. E., van der Valk, P., & Bø, L.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Haukeland University Hospital (NO)
- ORCID
- Bø, Lars
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-04
- Volume
- 66
- Issue
- 4
- Pages
- 321-328
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W1968478844
- Cited by
- 187
- References
- 31
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 8 · 2017: 16 · 2016: 7 · 2015: 11 · 2014: 12 · 2013: 12 · 2012: 18
- FWCI
- 7.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- 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
- blood-brain barrier, multiple sclerosis, gray matter lesions, white matter lesions, plasma protein leakage, basement membrane, type IV collagen, astrocyte activation, tight junctions, endothelial cells, cortical lesions
- MeSH terms
- Adult, Aged, Basement Membrane, Blood-Brain Barrier, Cerebral Cortex, Female, Fibrinogen, Glial Fibrillary Acidic Protein, Humans, Immunoglobulin G, Immunohistochemistry, Male, Membrane Proteins, Middle Aged, Multiple Sclerosis, Tight Junctions, Collagen Type V, Claudin-5
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