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Cited by 99Multiple Sclerosis Research StudiesBarrier Structure and Function StudiesNeuroinflammation and Neurodegeneration Mechanisms

Loss of Blood-Brain Barrier Integrity in the Spinal Cord Is Common to Experimental Allergic Encephalomyelitis in Knockout Mouse Models

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Fabis, Marzena J., Scott, Gwen S., Kean, Rhonda B., Koprowski, Hilary, Hooper, D. Craig·2007·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0701252104PMC PMC1838442
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Abstract

Experimental allergic encephalomyelitis (EAE) is an inflammatory demyelinating disease of the CNS that is used to model certain parameters of multiple sclerosis. To establish the relative contributions of T cell reactivity, the loss of blood-brain barrier (BBB) integrity, CNS inflammation, and lesion formation toward the pathogenesis of EAE, we assessed the incidence of EAE and these parameters in mice lacking NF-kappaB, TNF-alpha, IFN-alphabeta receptors, IFN-gamma receptors, and inducible nitric oxide synthase. Although increased myelin oligodendrocyte glycoprotein-specific T cell reactivity was generally associated with a more rapid onset or increased disease severity, the loss of BBB integrity and cell accumulation in spinal cord tissues was invariably associated with the development of neurological disease signs. Histological and real-time RT-PCR analyses revealed differences in the nature of immune/inflammatory cell accumulation in the spinal cord tissues of the different mouse strains. On the other hand, disease severity during the acute phase of EAE directly correlated with the extent of BBB permeability. Thus, the loss of BBB integrity seems to be a requisite event in the development of EAE and can occur in the absence of important inflammatory mediators.

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Crossref · 10.1073/pnas.0701252104

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  • The severity of symptoms for MS and AD has been shown to be tightly coupled with BBB integrity, with onset and progression correlating strongly with BBB disruption.

    “the severity of symptoms for MS and AD have been shown to be tightly coupled with BBB integrity, with research indicating that onset and progression of symptoms correlates strongly with BBB disruption”

    From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Fabis et al., 2007

    The Results report a close correlation between BBB permeability and clinical severity in mice with EAE (r² = 0.989), and the Discussion associates permeability changes with the appearance of EAE signs. The paper describes EAE as a model of certain features of MS, but these findings do not establish a strong correlation with symptom onset and progression in people with MS; the supplied passages do not address AD. Page numbers were not provided. (LLM, conf=0.89)

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Research works printed but not linked: 8

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Authors
Fabis, M. J., Scott, G. S., Kean, R. B., Koprowski, H., & Hooper, D. C.
Affiliations
  • *Center for Neurovirology, Department of Cancer Biology,
  • Thomas Jefferson University (US)
ORCID
Hooper, D. Craig
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2007-03-27
Volume
104
Issue
13
Pages
5656-5661
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0701252104
PMC
PMC1838442
OpenAlex
W2036469393
Cited by
99
References
49
Citations by year
2026: 2 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 7 · 2018: 6 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 7 · 2012: 4
FWCI
5.91
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
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
experimental autoimmune encephalomyelitis, blood-brain barrier integrity, spinal cord, multiple sclerosis, demyelination, NF-κB, TNF-α, IFN-alpha/beta receptor, IFN-gamma receptor, inducible nitric oxide synthase, neuroinflammation, disease severity, knockout mouse models
MeSH terms
Animals, Blood-Brain Barrier, Central Nervous System, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Interferon-gamma, Male, Permeability, Sex Factors, Spinal Cord, T-Lymphocytes, Mice, Knockout, Cell Proliferation, Mice

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