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Cited by 135Barrier Structure and Function StudiesTraumatic Brain Injury ResearchTraumatic Brain Injury and Neurovascular Disturbances

Blood–Brain Barrier Dysfunction as a Hallmark Pathology in Chronic Traumatic Encephalopathy

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Doherty, Colin P., O’Keefe, Eoin, Wallace, Eugene, Loftus, Teresa, Keaney, James, Kealy, John, Humphries, Marian M., Molloy, Michael G. +3 more·2016·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/nlw036PMC PMC4913433
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Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition associated with repetitive mild traumatic brain injury. In recent years, attention has focused on emerging evidence linking the development of CTE to concussive injuries in athletes and military personnel; however, the underlying molecular pathobiology of CTE remains unclear. Here, we provide evidence that the blood-brain barrier (BBB) is disrupted in regions of dense perivascular p-Tau accumulation in a case of CTE. Immunoreactivity patterns of the BBB-associated tight junction components claudin-5 and zonula occludens-1 were markedly discontinuous or absent in regions of perivascular p-Tau deposition; there was also immunohistochemical evidence of a BBB in these foci. Because the patient was diagnosed premortem clinically as having progressive supranuclear palsy (PSP), we also compromised that the CTE alterations appear to be distinct from those in the brain of a patient with PSP. This report represents the first description of BBB dysfunction in a pathologically proven CTE case and suggests a vascular component in the postconcussion cascade of events that may ultimately lead to development of a progressive degenerative disorder. BBB dysfunction may represent a correlate of neural dysfunction in live subjects suspected of being at risk for development of CTE.

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  • Post mortem chronic traumatic encephalopathy studies reveal cerebral edema, perivascular hemosiderin-burdened macrophages, mural cell mineralization, enlarged perivascular spaces, and leukocyte infiltration.

    “Post mortem CTE studies reveal cerebral edema, perivascular hemosiderinburdened macrophages, mural cell mineralization, enlarged perivascular spaces, and leukocyte infiltration (149, 325, 454, 455)”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [149]

    The Results report perivascular hemosiderin deposition in a postmortem CTE case, but do not identify hemosiderin-burdened macrophages. The Discussion associates cerebral edema with severe TBI, not with the CTE case; our copy does not report mural cell mineralization, enlarged perivascular spaces, or leukocyte infiltration in CTE. Page numbers are unavailable in the indexed passages. (LLM, conf=0.88)

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Research works printed but not linked: 14

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Sorted by citations

Authors
Doherty, C. P., O’Keefe, E., Wallace, E., Loftus, T., Keaney, J., Kealy, J., Humphries, M. M., Molloy, M. G., Meaney, J. F., Farrell, M., & Campbell, M.
Affiliations
Trinity College Dublin (IE)
ORCID
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2016-05-31
Volume
75
Issue
7
Pages
656-662
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1093/jnen/nlw036
PMC
PMC4913433
OpenAlex
W2412108891
Cited by
135
References
2
Citations by year
2026: 10 · 2025: 13 · 2024: 13 · 2023: 13 · 2022: 17 · 2021: 15 · 2020: 24 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 1
FWCI
5.48
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
chronic traumatic encephalopathy, blood-brain barrier dysfunction, phosphorylated tau, claudin-5, zonula occludens-1, tight junctions, progressive supranuclear palsy, repetitive mild traumatic brain injury, vascular pathology
MeSH terms
Chronic Traumatic Encephalopathy, Blood-Brain Barrier, Humans, Male, Middle Aged, Fatal Outcome, Brain Injury, Chronic

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