ArticleProceedings of the National Academy of Sciences of the United States of America2018
Contributions of the glycocalyx, endothelium, and extravascular compartment to the blood-brain barrier.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
162 citing papers in PubMed, 1 synthesis or guideline pooled it, 237 citations in OpenAlex.
- Pooled it
- High Level of Serum and Cerebrospinal Fluid of Heparan Sulfate and Hyaluronic Acid Might Be a Biomarker of Severity of Neuromyelitis Optica.Frontiers in immunology · 2021Trial
- Huntington's disease vasculopathy is barrier-type-selective and arteriolar-dominant with spatially-coupled astrogliosis and reversible by S1pr1 stimulation.Nature communications · 2026Article
- Biomedical Materials and Fabrication Methods for Construction of In Vitro Neurovascular Unit Models.Materials (Basel, Switzerland) · 2026Review
- Glycation at the Gate: A Brain Endothelial Glycocalyx Model and Therapeutic Roadmap for Alzheimer's Disease.Biomedicines · 2026Article
- Diagnostic Value of Glycocalyx Shedding in Blood for Differentiating between Parkinson's Disease and Multiple System Atrophy.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption.Cell death & disease · 2026Article
- A Age Related Vascular Senescence: Mystery of Blood-brain Barrier Dysfunction in Neurodegeneration.Molecular neurobiology · 2026Review
- Glycocalyx and basal lamina in neurological disorders.Matrix biology : journal of the International Society for Matrix Biology · 2026Review
- Biomimetic flowing vessel-on-a-chip recruiting glycocalyx features for investigating dexmedetomidine function.Materials today. Bio · 2026Article
- Strategies for blood-brain barrier rejuvenation and repair.Nature reviews. Drug discovery · 2026Review
- Cardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Nitric Oxide-S-Nitrosylation and Its Role in Neuroinflammation Associated with Neuropsychiatric Conditions.International journal of molecular sciences · 2026Review
- The Role of Cytokines in Vascular Endothelial Glycocalyx Integrity and Impairment Following Open-Heart Surgery.Biomedicines · 2026Review
- Review
- Development of the blood-brain barrier.Development (Cambridge, England) · 2026Review
- Brain Endothelial Glycocalyx as a Blood-Facing Translational Interface in Alzheimer's Disease: Beyond "Leaky" Barriers Toward Repair-First Stratification.Drug design, development and therapy · 2026Review
- Engineering 3D neural models of neurodegeneration: the Neural Microenvironment Design Code (NMDC), design principles, and emerging new approach methodologies.NAM journal · 2026Review
- Immunotherapy-associated dysgraphia as an early neurocognitive manifestation of immune effector cell-associated neurotoxicity syndrome: clinical characteristics, mechanistic insights, and assessment challenges.Frontiers in immunology · 2026Review
- Comparative permeability of the blood-brain barrier to albumin, DTPA, and sucrose: effects of inflammation-induced disruption.Fluids and barriers of the CNS · 2025Article
102 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endothelial cells that form the blood-brain barrier (BBB) are coated with glycocalyx, on the luminal side, and with the basement membrane and astrocyte endfeet, on the abluminal side. However, it is unclear how exactly the glycocalyx and extravascular structures contribute to BBB properties. We used two-photon microscopy in anesthetized mice to record passive transport of four different-sized molecules-sodium fluorescein (376 Da), Alexa Fluor (643 Da), 40-kDa dextran, and 150-kDa dextran-from blood to brain, at the level of single cortical capillaries. Both fluorescein and Alexa penetrated nearly the entire glycocalyx volume, but the dextrans penetrated less than 60% of the volume. This suggested that the glycocalyx was a barrier for large but not small molecules. The estimated permeability of the endothelium was the same for fluorescein and Alexa but several-fold lower for the larger dextrans. In the extravascular compartment, co-localized with astrocyte endfeet, diffusion coefficients of the dyes were an order of magnitude lower than in the brain parenchyma. This suggested that the astrocyte endfeet and basement membrane also contributed to BBB properties. In conclusion, the passive transport of small and large hydrophilic molecules through the BBB was determined by three separate barriers: the glycocalyx, the endothelium, and the extravascular compartment. All three barriers must be taken into account in drug delivery studies and when considering BBB dysfunction in disease states.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.