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Neuronal regulation of the blood–brain barrier and neurovascular coupling

Nature Reviews Neuroscience volume 21, pages 416–432 (2020)Cite this article

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Abstract

To continuously process neural activity underlying sensation, movement and cognition, the CNS requires a homeostatic microenvironment that is not only enriched in nutrients to meet its high metabolic demands but that is also devoid of toxins that might harm the sensitive neural tissues. This highly regulated microenvironment is made possible by two unique features of CNS vasculature absent in the peripheral organs. First, the blood–blood barrier, which partitions the circulating blood from the CNS, acts as a gatekeeper to facilitate the selective trafficking of substances between the blood and the parenchyma. Second, neurovascular coupling ensures that, following local neural activation, regional blood flow is increased to quickly supply more nutrients and remove metabolic waste. Here, we review how neural and vascular activity act on one another with regard to these two properties.

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Fig. 1: The neurovascular unit and cerebrovascular anatomy.
Fig. 2: Properties of the BBB.
Fig. 3: The direct pathway to elicit neurovascular coupling.
Fig. 4: The endothelium-dependent model of neurovascular coupling.

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Acknowledgements

The authors thank all the Gu laboratory members for reading and providing feedback on the Review. This work was supported by a Quan Fellowship (B.W.C.), a Mahoney Postdoctoral Fellowship (L.K.), a US National Institutes of Health Pioneer Award (DP1-NS092473 to C.G.), The Paul G. Allen Frontiers Group, Allen Distinguished Investigator (C.G.), NIH/NIDA, BRAIN Initiative Grant (C.G.) and the Fidelity Biosciences Research Initiative (C.G.). The research of C.G. was also supported in part by a Faculty Scholar grant from the Howard Hughes Medical Institute.

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  1. These authors contributed equally: Luke Kaplan, Brian W. Chow.

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  1. Department of Neurobiology, Harvard Medical School, Boston, MA, USA

    Luke Kaplan, Brian W. Chow & Chenghua Gu

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All authors researched data for the article, contributed substantially to discussion of the article’s content, wrote the article, and reviewed and edited the manuscript before submission.

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Correspondence to Chenghua Gu.

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Competing interests

This research was funded by the Fidelity Biosciences Research Initiative. C.G. is listed as a co-inventor on the following patent application: ‘Methods and compositions relating to modulation of the permeability of the blood–brain barrier’, inventors C.G. and A. Ben-Zvi; US Patent Application 14/897,264.

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Nature Reviews Neuroscience thanks S. Liebner and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Blood–brain barrier

(BBB). A physiological barrier formed by CNS endothelial cells to regulate the trafficking of molecules between the blood and the brain.

Neurovascular coupling

(NVC). The process by which local neural activation can rapidly increase local blood flow; it is the basis of functional MRI.

Mural cell

A collective term to describe the cell types that wrap around blood vessels, including the smooth muscle cells on arteries and pericytes on capillaries

Caveolae

Flask-shaped vesicular structures formed by caveolins, approximately 70 nm in diameter.

Diphtheria toxin

A toxin that inhibits protein synthesis, leading to cell death.

Angiogenesis

Growth of new blood vessels from existing blood vessels.

Circumventricular organs

(CVOs). Midline brain structures with permeable vasculature allowing ready exchange of molecules between neurons and the blood.

Polyinosinic:polycytidylic acid

Synthetic mimic of double-stranded RNA mimicking the effect of viral infection on the immune system.

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Kaplan, L., Chow, B.W. & Gu, C. Neuronal regulation of the blood–brain barrier and neurovascular coupling. Nat Rev Neurosci 21, 416–432 (2020). https://doi.org/10.1038/s41583-020-0322-2

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