Novel insights into the development and maintenance of the blood-brain barrier
Open accessAbstract
The blood-brain barrier (BBB) is essential for maintaining homeostasis within the central nervous system (CNS) and is a prerequisite for proper neuronal function. The BBB is localized to microvascular endothelial cells that strictly control the passage of metabolites into and out of the CNS. Complex and continuous tight junctions and lack of fenestrae combined with low pinocytotic activity make the BBB endothelium a tight barrier for water soluble moleucles. In combination with its expression of specific enzymes and transport molecules, the BBB endothelium is unique and distinguishable from all other endothelial cells in the body. During embryonic development, the CNS is vascularized by angiogenic sprouting from vascular networks originating outside of the CNS in a precise spatio-temporal manner. The particular barrier characteristics of BBB endothelial cells are induced during CNS angiogenesis by cross-talk with cellular and acellular elements within the developing CNS. In this review, we summarize the currently known cellular and molecular mechanisms mediating brain angiogenesis and introduce more recently discovered CNS-specific pathways (Wnt/β-catenin, Norrin/Frizzled4 and hedgehog) and molecules (GPR124) that are crucial in BBB differentiation and maturation. Finally, based on observations that BBB dysfunction is associated with many human diseases such as multiple sclerosis, stroke and brain tumors, we discuss recent insights into the molecular mechanisms involved in maintaining barrier characteristics in the mature BBB endothelium.
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Bacterial products and metabolites can pass the blood-brain barrier and shape CNS development and functions and the genesis of certain diseases.
“Among the molecules that can pass the BBB are also bacterial products and metabolites shaping not only the CNS development and functions (6, 15) but also the genesis of certain diseases (33–42).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [33]
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- Authors
- Engelhardt, B., & Liebner, S.
- Affiliations
- University of Bern (CH)
- University Hospital Frankfurt (DE)
- Corresponding author
- Engelhardt, Britta
- Liebner, Stefan
- Venue
- Cell and Tissue Research
- Published
- 2014-03
- Volume
- 355
- Issue
- 3
- Pages
- 687-699
- ISSN
- 0302-766X (ISSN-L)
- 1432-0878
- PMC
- PMC3972432
- OpenAlex
- W2055823942
- Cited by
- 313
- References
- 111
- Citations by year
- 2026: 20 · 2025: 19 · 2024: 23 · 2023: 21 · 2022: 24 · 2021: 35 · 2020: 30 · 2019: 35 · 2018: 24 · 2017: 22 · 2016: 20 · 2015: 26 · 2014: 13 · 2012: 1
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Cell and Tissue Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- BORIS (University Library Bern) (submittedVersion, cc-by)
- Open Access CRIS of the University of Bern
- Funders
- European Commission (241861)
- 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 › Angiogenesis and VEGF in Cancer
- Keywords
- blood-brain barrier, tight junctions, Wnt/β-catenin signaling, Hedgehog signaling, GPR124, BBB dysfunction, multiple sclerosis, stroke, brain tumors, endothelial differentiation
- MeSH terms
- Animals, Blood-Brain Barrier, Cell Differentiation, Humans, Signal Transduction, Tight Junctions, beta Catenin, Wnt Signaling Pathway
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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