Dispersion as a waste-clearance mechanism in flow through penetrating perivascular spaces in the brain

Daniel E. Troyetsky; Jeffrey Tithof; John H. Thomas; Douglas H. Kelley

doi:10.1038/s41598-021-83951-1

Dispersion as a waste-clearance mechanism in flow through penetrating perivascular spaces in the brain

Daniel E. Troyetsky, Jeffrey Tithof, John H. Thomas, Douglas H. Kelley

Mechanical Engineering

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Accumulation of metabolic wastes in the brain is correlated with several neurodegenerative disorders, including Alzheimer’s disease. Waste transport and clearance occur via dispersion, the combined effect of diffusion and advection by flow of fluid. We examine the relative contributions of diffusion and advection in the perivascular spaces (PVSs) that surround penetrating cortical blood vessels and are filled with cerebrospinal fluid (CSF). To do so, we adapt prior analytic predictions of dispersion to the context of PVSs. We also perform advection-diffusion simulations in PVS-like geometries with parameters relevant to transport of amyloid-β (associated with Alzheimer’s) in a variety of flows, motivated by in vivo measurements. Specifically, we examine solute transport in steady and unsteady Poiseuille flows in an open (not porous) concentric circular annulus. We find that a purely oscillatory flow enhances dispersion only weakly and does not produce significant transport, whereas a steady flow component, even if slow, clears waste more effectively.

Original language	English (US)
Article number	4595
Journal	Scientific reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-83951-1
State	Published - Feb 25 2021

Bibliographical note

Funding Information:
This work was supported by the NIH National Institute of Aging (Grant RF1AG057575) and by the US Army Research Office (Grant MURI W911NF1910280). J. Tithof was also supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. The authors are grateful for fruitful conversations with M. Nedergaard and J. Liu, and for expert illustration by D. Xue.

Publisher Copyright:
© 2021, The Author(s).

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

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abstract = "Accumulation of metabolic wastes in the brain is correlated with several neurodegenerative disorders, including Alzheimer{\textquoteright}s disease. Waste transport and clearance occur via dispersion, the combined effect of diffusion and advection by flow of fluid. We examine the relative contributions of diffusion and advection in the perivascular spaces (PVSs) that surround penetrating cortical blood vessels and are filled with cerebrospinal fluid (CSF). To do so, we adapt prior analytic predictions of dispersion to the context of PVSs. We also perform advection-diffusion simulations in PVS-like geometries with parameters relevant to transport of amyloid-β (associated with Alzheimer{\textquoteright}s) in a variety of flows, motivated by in vivo measurements. Specifically, we examine solute transport in steady and unsteady Poiseuille flows in an open (not porous) concentric circular annulus. We find that a purely oscillatory flow enhances dispersion only weakly and does not produce significant transport, whereas a steady flow component, even if slow, clears waste more effectively.",

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N2 - Accumulation of metabolic wastes in the brain is correlated with several neurodegenerative disorders, including Alzheimer’s disease. Waste transport and clearance occur via dispersion, the combined effect of diffusion and advection by flow of fluid. We examine the relative contributions of diffusion and advection in the perivascular spaces (PVSs) that surround penetrating cortical blood vessels and are filled with cerebrospinal fluid (CSF). To do so, we adapt prior analytic predictions of dispersion to the context of PVSs. We also perform advection-diffusion simulations in PVS-like geometries with parameters relevant to transport of amyloid-β (associated with Alzheimer’s) in a variety of flows, motivated by in vivo measurements. Specifically, we examine solute transport in steady and unsteady Poiseuille flows in an open (not porous) concentric circular annulus. We find that a purely oscillatory flow enhances dispersion only weakly and does not produce significant transport, whereas a steady flow component, even if slow, clears waste more effectively.

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Dispersion as a waste-clearance mechanism in flow through penetrating perivascular spaces in the brain

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