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A network model of glymphatic flow under different experimentally-motivated parametric scenarios

View ORCID ProfileJeffrey Tithof, View ORCID ProfileKimberly A. S. Boster, View ORCID ProfilePeter A. R. Bork, View ORCID ProfileMaiken Nedergaard, View ORCID ProfileJohn H. Thomas, View ORCID ProfileDouglas H. Kelley
doi: https://doi.org/10.1101/2021.09.23.461519
Jeffrey Tithof
1Department of Mechanical Engineering, University of Rochester, Rochester, NY 14627, USA
2Department of Mechanical Engineering, University of Minnesota, Minneapolis, MN 55455, USA
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  • For correspondence: tithof@umn.edu
Kimberly A. S. Boster
1Department of Mechanical Engineering, University of Rochester, Rochester, NY 14627, USA
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Peter A. R. Bork
3Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
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Maiken Nedergaard
3Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
4Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY 14642, USA
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John H. Thomas
1Department of Mechanical Engineering, University of Rochester, Rochester, NY 14627, USA
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Douglas H. Kelley
1Department of Mechanical Engineering, University of Rochester, Rochester, NY 14627, USA
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Abstract

Rapidly growing evidence demonstrates that flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) – annular tunnels surrounding vasculature in the brain – is a critically-important component of neurophysiology. CSF inflow contributes during physiological conditions to clearance of metabolic waste and in pathological situations to edema formation. However, brain-wide imaging methods cannot resolve PVSs, and high-resolution methods cannot access deep tissue or be applied to human subjects, so theoretical models provide essential insight. We model this CSF pathway as a network of hydraulic resistances, built from published parameters. A few parameters have very wide uncertainties, so we focus on the limits of their feasible ranges by analyzing different parametric scenarios. We identify low-resistance PVSs and high-resistance parenchyma (brain tissue) as the scenario that best explains experimental observations. Our results point to the most important parameters that should be measured in future experiments. Extensions of our modeling may help predict stroke severity or lead to neurological disease treatments and drug delivery methods.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 24, 2021.
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A network model of glymphatic flow under different experimentally-motivated parametric scenarios
Jeffrey Tithof, Kimberly A. S. Boster, Peter A. R. Bork, Maiken Nedergaard, John H. Thomas, Douglas H. Kelley
bioRxiv 2021.09.23.461519; doi: https://doi.org/10.1101/2021.09.23.461519
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A network model of glymphatic flow under different experimentally-motivated parametric scenarios
Jeffrey Tithof, Kimberly A. S. Boster, Peter A. R. Bork, Maiken Nedergaard, John H. Thomas, Douglas H. Kelley
bioRxiv 2021.09.23.461519; doi: https://doi.org/10.1101/2021.09.23.461519

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