TY - JOUR

T1 - Perivascular pumping in the mouse brain

T2 - Improved boundary conditions reconcile theory, simulation, and experiment

AU - Ladrón-de-Guevara, Antonio

AU - Shang, Jessica K.

AU - Nedergaard, Maiken

AU - Kelley, Douglas H.

N1 - Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022

Y1 - 2022

N2 - Cerebrospinal fluid (CSF) flows through the perivascular spaces (PVSs) surrounding cerebral arteries. Revealing the mechanisms driving that flow could bring improved understanding of brain waste transport and insights for disorders including Alzheimer's disease and stroke. In vivo velocity measurements of CSF in surface PVSs in mice have been used to argue that flow is driven primarily by the pulsatile motion of artery walls — perivascular pumping. However, fluid dynamics theory and simulation have predicted that perivascular pumping produces flows differing from in vivo observations starkly, particularly in the phase and relative amplitude of flow oscillation. We show that coupling theoretical and simulated flows to more realistic end boundary conditions, using resistance and compliance values measured in mice instead of using periodic boundaries, results in velocities that match observations more closely in phase and relative amplitude of oscillation, while preserving the existing agreement in mean flow speed. This quantitative agreement among theory, simulation, and in vivo measurement further supports the idea that perivascular pumping is an important CSF driver in physiological conditions.

AB - Cerebrospinal fluid (CSF) flows through the perivascular spaces (PVSs) surrounding cerebral arteries. Revealing the mechanisms driving that flow could bring improved understanding of brain waste transport and insights for disorders including Alzheimer's disease and stroke. In vivo velocity measurements of CSF in surface PVSs in mice have been used to argue that flow is driven primarily by the pulsatile motion of artery walls — perivascular pumping. However, fluid dynamics theory and simulation have predicted that perivascular pumping produces flows differing from in vivo observations starkly, particularly in the phase and relative amplitude of flow oscillation. We show that coupling theoretical and simulated flows to more realistic end boundary conditions, using resistance and compliance values measured in mice instead of using periodic boundaries, results in velocities that match observations more closely in phase and relative amplitude of oscillation, while preserving the existing agreement in mean flow speed. This quantitative agreement among theory, simulation, and in vivo measurement further supports the idea that perivascular pumping is an important CSF driver in physiological conditions.

KW - Brain

KW - Cerebrospinal fluid

KW - Compliance

KW - Glymphatic system

KW - Hydraulic resistance

KW - Perivascular pumping

U2 - 10.1016/j.jtbi.2022.111103

DO - 10.1016/j.jtbi.2022.111103

M3 - Journal article

C2 - 35339513

AN - SCOPUS:85127220425

VL - 542

JO - Journal of Theoretical Biology

JF - Journal of Theoretical Biology

SN - 0022-5193

M1 - 111103

ER -