Novel insights into the development and maintenance of the blood-brain barrier

Engelhardt, Britta; Liebner, Stefan (2014). Novel insights into the development and maintenance of the blood-brain barrier. Cell and tissue research, 355(3), pp. 687-699. Springer 10.1007/s00441-014-1811-2

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0302-766X

Publisher:

Springer

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

07 Apr 2015 12:55

Last Modified:

08 Apr 2015 10:49

Publisher DOI:

10.1007/s00441-014-1811-2

PubMed ID:

24590145

BORIS DOI:

10.7892/boris.66359

URI:

https://boris.unibe.ch/id/eprint/66359

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