4.7 Review

Revisiting the neurovascular unit

Journal

NATURE NEUROSCIENCE
Volume 24, Issue 9, Pages 1198-1209

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41593-021-00904-7

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Funding

  1. NIH [R01-NS34179, R01-NS100447, R37-NS089323, R01-NS095441, R01-NS/HL37853]

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Schaeffer and Iadecola reviewed the heterogeneity of the neurovasculature and discussed the limitations of the neurovascular unit concept and the molecular diversity of cerebrovascular cells. They proposed the concept of a 'neurovascular complex' composed of segmentally diverse functional modules that implement coordinated vascular responses to central and peripheral signals.
Schaeffer and Iadecola review the anatomical, molecular and functional heterogeneity of the neurovasculature and highlight the coordinated interaction of factors intrinsic and extrinsic to the brain in its dynamic regulation and role in disease. 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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