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Cited by 1,168Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsIon Transport and Channel Regulation

Astrocyte-endothelial Interactions and Blood-Brain Barrier Permeability*

Abbott, N. Joan·2002·Journal of Anatomy
DOI 10.1046/j.1469-7580.2002.00064.x
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Abstract

The blood-brain barrier (BBB) is formed by brain endothelial cells lining the cerebral microvasculature, and is an important mechanism for protecting the brain from fluctuations in plasma composition, and from circulating agents such as neurotransmitters and xenobiotics capable of disturbing neural function. The barrier also plays an important role in the homeostatic regulation of the brain microenvironment necessary for the stable and co-ordinated activity of neurones. The BBB phenotype develops under the influence of associated brain cells, especially astrocytic glia, and consists of more complex tight junctions than in other capillary endothelia, and a number of specific transport and enzyme systems which regulate molecular traffic across the endothelial cells. Transporters characteristic of the BBB phenotype include both uptake mechanisms (e.g. GLUT-1 glucose carrier, L1 amino acid transporter) and efflux transporters (e.g. P-glycoprotein). In addition to a role in long-term barrier induction and maintenance, astrocytes and other cells can release chemical factors that modulate endothelial permeability over a time-scale of seconds to minutes. Cell culture models, both primary and cell lines, have been used to investigate aspects of barrier induction and modulation. Conditioned medium taken from growing glial cells can reproduce some of the inductive effects, evidence for involvement of diffusible factors. However, for some features of endothelial differentiation and induction, the extracellular matrix plays an important role. Several candidate molecules have been identified, capable of mimicking aspects of glial-mediated barrier induction of brain endothelium; these include TGFbeta, GDNF, bFGF, IL-6 and steroids. In addition, factors secreted by brain endothelial cells including leukaemia inhibitory factor (LIF) have been shown to induce astrocytic differentiation. Thus endothelium and astrocytes are involved in two-way induction. Short-term modulation of brain endothelial permeability has been shown for a number of small chemical mediators produced by astrocytes and other nearby cell types. It is clear that endothelial cells are involved in both long- and short-term chemical communication with neighbouring cells, with the perivascular end feet of astrocytes being of particular importance. The role of barrier induction and modulation in normal physiology and in pathology is discussed.

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  • Astrocytes communicate with endothelial cells and pericytes at the blood-brain barrier through their endfeet, which wrap along the surface of the endothelium and contribute to BBB structure.

    “Astrocytes communicate with endothelial cells and pericytes at the blood-brain barrier (BBB) through their endfeet,85 which wrap along the surface of the endothelium,86 and contribute to BBB structure.”

    From Uncovering the signatures of aging and senescence in the human dorsolateral prefrontal cortex (2026) · cites this paper as [85]

  • Endothelial tight junctions play a primary role in physical regulation of molecular transport at the blood-brain barrier and, with astrocytes, protect the brain from toxic xenobiotics.

    “Endothelial tight junctions also play a primary role in the physical regulation of molecular transport at the BBB, and working in conjunction with astrocytes, protect the brain from toxic xenobiotics (Figure 2; Abbott, 2002).”

    From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Abbott, 2002

  • Some compounds that are too lipophilic can be discharged after crossing into the brain by the P-glycoprotein efflux transporter.

    “Although lipophilicity is important for transmembrane diffusion through the BBB, some compounds that are too lipophilic can be discharged after crossing into the brain by the P-gp efflux transporter (Abbott, 2002; Banks, 2009).”

    From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Abbott, 2002

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Authors
Abbott, N. J.
Affiliations
King's College London (GB)
Corresponding author
Abbott, N. Joan
ORCID
Abbott, N. Joan
Venue
Journal of Anatomy
Publisher
Wiley
Published
2002-06
Volume
200
Issue
6
Pages
629-638
ISSN
  • 0021-8782 (ISSN-L)
  • 1469-7580
DOI
10.1046/j.1469-7580.2002.00064.x
OpenAlex
W2117691576
Cited by
1,168
References
73
Citations by year
2026: 19 · 2025: 38 · 2024: 43 · 2023: 54 · 2022: 60 · 2021: 67 · 2020: 74 · 2019: 52 · 2018: 59 · 2017: 63 · 2016: 59 · 2015: 45 · 2014: 50 · 2013: 45 · 2012: 51
FWCI
4.03
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 27 d)
Locations
  • Journal of Anatomy (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Funders
Wellcome Trust
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
blood-brain barrier, astrocytes, brain endothelial cells, astrocyte-endothelial interactions, endothelial permeability, tight junctions, conditioned medium, extracellular matrix, TGF-beta, glial cell line-derived neurotrophic factor, basic fibroblast growth factor, interleukin-6, steroids, leukemia inhibitory factor, astrocyte differentiation, chemical communication, brain microenvironment, P-glycoprotein, GLUT1
MeSH terms
Animals, Astrocytes, Blood-Brain Barrier, Capillary Permeability, Cell Communication, Cell Differentiation, Endothelium, Vascular, Humans, Intercellular Junctions

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