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

Florian Goirand (1) , Tanguy Le Borgne (1) , Sylvie Lorthois (2)

1 GR - Géosciences Rennes
2 IMFT - Institut de mécanique des fluides de Toulouse

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 amyloidβ, 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.

Domains: Fluid mechanics [physics.class-ph]; Neurons and Cognition [q-bio.NC]

Florian Goirand, Tanguy Le Borgne, Sylvie Lorthois. Network-driven anomalous transport is a fundamental component of brain microvascular dysfunction. Nature Communications, 2021, 12 (1), pp.7295. ⟨10.1038/s41467-021-27534-8⟩. ⟨insu-03557344⟩