Disruption of central nervous system barriers in multiple sclerosis
Open accessAbstract
The delicate microenvironment of the central nervous system (CNS) is protected by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCB). These barriers function in distinct CNS compartments and their anatomical basis lay on the junctional proteins present in endothelial cells for the BBB and in the choroidal epithelium for the BCB. During neuroinflammatory conditions like multiple sclerosis (MS) and its murine model experimental autoimmune encephalomyelitis (EAE), activation or damage of the various cellular components of these barriers facilitate leukocyte infiltration leading to oligodendrocyte death, axonal damage, demyelination and lesion development. This manuscript will review in detail the features of these barriers under physiological and pathological conditions, particularly when focal immune activation promotes the loss of the BBB and BCB phenotype, the upregulation of cell adhesion molecules (CAMs) and the recruitment of immune cells.
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Neuroimaging studies using gadolinium enhancement have established that blood-brain barrier disruption is an early feature of multiple sclerosis pathogenesis.
“Neuroimaging studies using gadolinium enhancement have established that BBB disruption is an early feature of MS pathogenesis (14).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [14]
Section 6 says BBB changes can be identified clinically by MRI and are thought to occur early in MS lesion formation. It does not say gadolinium-enhanced imaging established this finding; gadolinium appears in the title of a cited study in the References. The claim also states more certainty than the review’s 'thought to occur' wording. (LLM, conf=0.84)
Experimental — accuracy not yet measuredReduced levels of tight junction proteins were associated with fibrinogen leak and perivascular astrogliosis in multiple sclerosis.
“Reduced levels of TJ proteins were associated with fibrinogen leak and perivascular astrogliosis (14).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [14]
Section 6 (page unavailable) says junctional-protein abnormalities in MS lesions coincide with perivascular astrogliosis and serum-protein leakage. The Fig. 1 caption also describes decreased tight-junction protein expression and perivascular astrogliosis. The copy does not identify the leaked protein as fibrinogen, so that specificity is unsupported. (LLM, conf=0.88)
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References 227 · Cited by 334
Research works printed but not linked: 9
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- Authors
- Alvarez, J. I., Cayrol, R., & Prat, A.
- Affiliations
- Hôpital Notre-Dame (CA)
- Corresponding author
- Prat, Alexandre
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 1812
- Issue
- 2
- Pages
- 252-264
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W1985775190
- Cited by
- 334
- References
- 227
- Citations by year
- 2026: 7 · 2025: 26 · 2024: 23 · 2023: 12 · 2022: 21 · 2021: 29 · 2020: 25 · 2019: 21 · 2018: 18 · 2017: 24 · 2016: 18 · 2015: 26 · 2014: 17 · 2013: 23 · 2012: 23
- FWCI
- 1.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- multiple sclerosis, blood-brain barrier, blood-CSF barrier, experimental autoimmune encephalomyelitis, choroid plexus epithelium, adhesion molecules, leukocyte infiltration, demyelination, oligodendrocyte death, neuroinflammation, barrier disruption
- MeSH terms
- Animals, Blood-Brain Barrier, Encephalomyelitis, Autoimmune, Experimental, Humans, Intercellular Junctions, Leukocytes, Multiple Sclerosis, Cell Adhesion Molecules, Integrins, Chemokines, Selectins, Mice
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