Cited by 150Multiple Sclerosis Research StudiesBarrier Structure and Function StudiesNeuroinflammation and Neurodegeneration Mechanisms

Focal disturbances in the blood–brain barrier are associated with formation of neuroinflammatory lesions

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Alvarez, Jorge Ivan, Saint-Laurent, Olivia, Godschalk, Alisha, Terouz, Simone, Briels, Casper, Larouche, Sandra, Bourbonnière, Lyne, Larochelle, Catherine +1 more·2015·Neurobiology of Disease

Abstract

Early changes in the normal appearing white matter of multiple sclerosis (MS) patients precede the appearance of gadolinium-enhancing lesions. Although these findings suggest blood-brain barrier (BBB) breakdown as an important feature in MS pathogenesis, limited information is available on the BBB alterations during lesion genesis. Here, we perform a longitudinal characterization of the vascular, neuropathological and immunological changes before lesion formation in mice developing spontaneous relapsing-remitting experimental autoimmune encephalomyelitis (sRR-EAE). We found a significant upregulation of Th1 and Th17 cytokines in the periphery of sRR-EAE mice before any evident neuropathology. In the CNS, BBB and astroglial activations were the first pathological changes occurring after 45days of age and were followed by immune cell infiltration by day 50. These pathological alterations subsequently led to perivascular demyelination and disease onset. In MS, (p)reactive lesions mirrored the changes seen in early sRR-EAE by displaying considerable BBB disruption, perivascular astrogliosis, redistribution of junctional proteins and increased expression of endothelial cell adhesion molecules. Our findings suggest that BBB breach occurs before significant immune cell infiltration and demyelination. In addition, peripheral immune activation during sRR-EAE precedes CNS pathology, suggesting that outside in signaling mechanisms play a role in the development of neuroinflammatory lesi…

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Crossref · 10.1016/j.nbd.2014.09.016

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  • In spontaneous relapsing-remitting experimental autoimmune encephalomyelitis mice, blood-brain barrier disruption occurs before immune cell infiltration in focal lesions.

    “Longitudinal studies in spontaneous relapsing-remittingEAE mice have shown that BBB disruption occurs before immune cell infiltration in focal lesions (15).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [15]

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Authors
Alvarez, J. I., Saint-Laurent, O., Godschalk, A., Terouz, S., Briels, C., Larouche, S., Bourbonnière, L., Larochelle, C., & Prat, A.
Affiliations
Centre Hospitalier de l’Université de Montréal (CA)
Corresponding author
Alvarez, Jorge Ivan
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2015-02
Volume
74
Pages
14-24
ISSN
0969-9961 (ISSN-L)
OpenAlex
W1967948598
Cited by
150
References
50
Citations by year
2026: 7 · 2025: 10 · 2024: 15 · 2023: 15 · 2022: 15 · 2021: 20 · 2020: 9 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 11 · 2015: 9
FWCI
7.43
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Funders
Canadian Institutes of Health Research (MOP-81088)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
blood-brain barrier disruption, multiple sclerosis, experimental autoimmune encephalomyelitis, neuroinflammation, astroglial activation, Th1 cytokines, Th17 cytokines, reactive lesion, endothelial adhesion molecules, immune cell infiltration, outside-in signaling
MeSH terms
Adult, Aged, Animals, Astrocytes, Blood-Brain Barrier, Brain, Encephalomyelitis, Autoimmune, Experimental, Endothelium, Vascular, Female, Gliosis, Humans, Longitudinal Studies, Male, Mice, Transgenic, Middle Aged, T-Lymphocytes, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis, Relapsing-Remitting

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