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Contributions of the glycocalyx, endothelium, and extravascular compartment to the blood–brain barrier
Open accessAbstract
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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The barrier and interface mechanisms of the brain barrier, and brain drug delivery
Zhang, S., Gan, L., Cao, F., Wang, H., Gong, P., Ma, C., Ren, L., Lin, Y., & Lin, X. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.09.017 · Cited by 129
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A curious concept of CNS clearance
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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
- Publisher
- National Academy of Sciences
- Published
- 2018-09-14
- Volume
- 115
- Issue
- 40
- Pages
- E9429-E9438
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6176561
- 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
- bronze
- doi.org
- 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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