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Blood–brain barrier

Plugging the leak

Nature Reviews Neuroscience volume 11, page 789 (2010)Cite this article

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Daneman et al. showed first that in the rat and mouse cerebral cortex, endothelial cells express tight-junction molecules and the BBB-specific marker glucose transporter 1 (Glut1) as early as embryonic day 11. The low-molecular-mass tracer biotin, which is excluded from the CNS parenchyma by the BBB in postnatal animals, was also excluded from the brain in embryos as early as embryonic day 15. These data show that, contrary to the prevailing hypothesis that astrocytes induce the formation of the BBB postnatally, a functional BBB is present during embryogenesis, before astrocytes are generated.

The authors next set out to examine whether pericytes could be involved in the prenatal regulation of BBB function and structure. They studied Pdgfrb−/− mice, which lack CNS pericytes because beta-type platelet-derived growth factor receptor (PDGFRβ) signalling is essential for pericyte recruitment to developing vessels. These mice died at birth, and examination of the embryos showed that they had increased vascular permeability to biotin. In neonatal Pdgfrb hypomorph mice, the number of pericytes was inversely correlated with the permeability of the BBB, suggesting that pericytes are necessary for the proper formation of the BBB. The findings of the second paper, by Armulik et al., support the notion that pericytes are important in the regulation of the BBB. This group used adult, viable pericyte-deficient mice that had mutations in the PDGFB–PDGFRβ pathway, to show that pericyte deficiency increases the permeability of the BBB to water and to a range of tracers of different molecular masses.

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ORIGINAL RESEARCH PAPERS

  1. Daneman, R. et al. Pericytes are required for blood–brain barrier integrity during embryogenesis. Nature 13 Oct 2010 (doi 10.1038/nature09513)

  2. Armulik, A. et al. Pericytes regulate the blood–brain barrier. Nature 13 Oct 2010 (doi 10.1038/nature09522)

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  1. Ezzie Hutchinson
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Hutchinson, E. Plugging the leak. Nat Rev Neurosci 11, 789 (2010). https://doi.org/10.1038/nrn2954

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