Cited by 250Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsCerebrospinal fluid and hydrocephalus

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Contributions of the glycocalyx, endothelium, and extravascular compartment to the blood–brain barrier

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Kutuzov, Nikolay, Flyvbjerg, Henrik, Lauritzen, Martin·2018·Proceedings of the National Academy of Sciences

Abstract

Significance: The vascular endothelium constitutes the main barrier that restricts the transport of molecules from blood to brain. However, the barrier properties of structures adjacent to the vascular endothelium are understudied. Based on two-photon microscopy imaging of single cortical capillaries, we found that the blood–brain barrier (BBB) consisted of at least three elements: the endothelial glycocalyx, which forms a barrier on the blood side to large but not small molecules; the endothelium; and the basement membrane and astrocyte endfeet—the final line of defense on the brain side. All three elements restricted permeation of large molecules and should be taken into account when studying drug delivery and disease states.

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  • Unconjugated Alexa Fluor crosses the blood-brain barrier (BBB), invalidating its use for studying parenchymal diffusion.

    “Unconjugated Alexa Fluor crosses the blood–brain barrier (BBB), invalidating its use for studying parenchymal diffusion14.”

    From A curious concept of CNS clearance (2025) · cites this paper as [14]

    The Materials section identifies AF 488 as a dye injected intravenously, and Permeability of the Vascular Endothelium reports that AF crossed the endothelium. The Discussion says fluorescence from multiple blood vessels prevented the authors from analyzing parenchymal diffusion with their approach. It does not say that BBB crossing invalidates Alexa Fluor for studying parenchymal diffusion generally; it also describes dye injection through a pipette as a way to estimate it. Our copy provides no page numbers for these passages. (LLM, conf=0.86)

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Metadata

Authors
Kutuzov, N., Flyvbjerg, H., & Lauritzen, M.
Affiliations
  • University of Copenhagen (DK)
  • Technical University of Denmark (DK)
Corresponding author
Lauritzen, Martin
Venue
Proceedings of the National Academy of Sciences
Published
2018-09-14
Volume
115
Issue
40
Pages
E9429-E9438
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2891697907
Cited by
250
References
7
Citations by year
2026: 34 · 2025: 29 · 2024: 32 · 2023: 32 · 2022: 36 · 2021: 40 · 2020: 28 · 2019: 18 · 2018: 1
FWCI
9.50
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
Funders
  • Lundbeckfonden (107620)
  • Novo Nordisk (110159)
  • Forskningsstyrelsen (111165)
  • CESA (1070011011)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
Keywords
blood-brain barrier, glycocalyx, endothelial permeability, astrocyte endfeet, basement membrane, passive diffusion, dextran, fluorescein, diffusion coefficient, BBB dysfunction, drug delivery
MeSH terms
Animals, Biological Transport, Active, Blood-Brain Barrier, Carbocyanines, Endothelium, Vascular, Male, Glycocalyx, Fluorescein, Microscopy, Fluorescence, Multiphoton, Mice

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