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Control of low flow regions in the cortical vasculature determines optimal arterio-venous ratios - pnas.org

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Significance

Lacking any ability to store glucose, the mammalian brain relies on a constant glucose and oxygen supply via the cerebral vasculature. In the cortex, this supply is maintained by parallel arterioles and venules. Yet, mathematical modeling of both real and idealized cortical networks shows that, far from being perfused uniformly, the cortex is strewn with regions of very low flow. Increasing the number of perfusing vessels increases the number of low-flow spots. Minimizing the influence of low-flow spots sets an optimal arteriole–venule ratio that we find to be closely recapitulated in data from real mammalian cortices. Further, low-flow regions complicate the regulation of metabolite delivery with neuronal activity, leading to unintuitive changes in perfusion when penetrating vessels dilate.

Abstract

The energy demands of neurons are met by a constant supply of glucose and oxygen via the cerebral vasculature. The cerebral cortex is perfused by dense, parallel arterioles and venules, consistently in imbalanced ratios. Whether and how arteriole–venule arrangement and ratio affect the efficiency of energy delivery to the cortex has remained an unanswered question. Here, we show by mathematical modeling and analysis of the mapped mouse sensory cortex that the perfusive efficiency of the network is predicted to be limited by low-flow regions produced between pairs of arterioles or pairs of venules. Increasing either arteriole or venule density decreases the size of these low-flow regions, but increases their number, setting an optimal ratio between arterioles and venules that matches closely that observed across mammalian cortical vasculature. Low-flow regions are reshaped in complex ways by changes in vascular conductance, creating geometric challenges for matching cortical perfusion with neuronal activity.

Footnotes

  • Author contributions: Y.Q. and M.R. designed research, performed research, contributed new reagents/analytic tools, analyzed data, and wrote the paper.

  • The authors declare no competing interest.

  • This article is a PNAS Direct Submission. M.P.B. is a guest editor invited by the Editorial Board.

  • This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2021840118/-/DCSupplemental.

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