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Network-driven anomalous transport is a fundamental component of brain microvascular dysfunction

Goirand, Florian and Le Borgne, Tanguy and Lorthois, Sylvie Network-driven anomalous transport is a fundamental component of brain microvascular dysfunction. (2021) Nature Communications, 12 (7295). 1-12. ISSN 2041-1723

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Official URL: https://doi.org/10.1038/s41467-021-27534-8

Abstract

Blood microcirculation supplies neurons with oxygen and nutrients, and contributes to clearing their neurotoxic waste, through a dense capillary network connected to larger treelike vessels. This complex microvascular architecture results in highly heterogeneous blood flow and travel time distributions, whose origin and consequences on brain pathophysiology are poorly understood. Here, we analyze highly-resolved intracortical blood flow and transport simulations to establish the physical laws governing the macroscopic transport properties in the brain micro-circulation. We show that network-driven anomalous transport leads to the emergence of critical regions, whether hypoxic or with high concentrations of amyloid-β, a waste product centrally involved in Alzheimer’s Disease. We develop a Continuous-Time Random Walk theory capturing these dynamics and predicting that such critical regions appear much earlier than anticipated by current empirical models under mild hypoperfusion. These findings provide a framework for understanding and modelling the impact of microvascular dysfunction in brain diseases, including Alzheimer’s Disease.

Item Type:Article
Additional Information:Thanks to Nature editor. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
Other partners > Université de Rennes 1 (FRANCE)
Laboratory name:
Funders:
European Research Council - ERC - European Research Council - ERC
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Deposited On:12 Jan 2022 16:47

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