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Revisiting the neurovascular unit

Nature Neuroscience volume 24, pages 1198–1209 (2021)Cite this article

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Abstract

The brain is supplied by an elaborate vascular network that originates extracranially and reaches deep into the brain. The concept of the neurovascular unit provides a useful framework to investigate how neuronal signals regulate nearby microvessels to support the metabolic needs of the brain, but it does not consider the role of larger cerebral arteries and systemic vasoactive signals. Furthermore, the recently emerged molecular heterogeneity of cerebrovascular cells indicates that there is no prototypical neurovascular unit replicated at all levels of the vascular network. Here, we examine the cellular and molecular diversity of the cerebrovascular tree and the relative contribution of systemic and brain-intrinsic factors to neurovascular function. Evidence supports the concept of a ‘neurovascular complex’ composed of segmentally diverse functional modules that implement coordinated vascular responses to central and peripheral signals to maintain homeostasis of the brain. This concept has major implications for neurovascular regulation in health and disease and for brain imaging.

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Fig. 1: Anatomy of the large vessels supplying the brain.
Fig. 2: Segmental heterogeneity of cerebral arteries and diversity of vascular and perivascular cells.
Fig. 3: Endothelial expression heatmap and scatter plot of differentially expressed genes in the neocortex and the hippocampus.
Fig. 4: Local and remote vascular components of NVC.
Fig. 5: Sources and targets of brain intrinsic vasoactive signals.
Fig. 6: Central and peripheral vasoactive signals regulating CBF.

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Acknowledgements

We thank A. Gupta for providing the image of human brain vessel (Fig. 1a) and J. Anrather for input on the transcriptomics analysis. Supported by NIH grants R01-NS34179, R01-NS100447, R37-NS089323, R01-NS095441 and R01-NS/HL37853 to C.I.

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  1. Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA

    Samantha Schaeffer & Costantino Iadecola

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  1. Samantha Schaeffer
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C.I. and S.S. wrote the manuscript and prepared the figures. S.S. performed the analysis of RNA-seq data.

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Correspondence to Costantino Iadecola.

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C.I. serves on the Scientific Advisory Board of Broadview Ventures. S.S. has no conflicts to declare.

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Schaeffer, S., Iadecola, C. Revisiting the neurovascular unit. Nat Neurosci 24, 1198–1209 (2021). https://doi.org/10.1038/s41593-021-00904-7

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