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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A network model of glymphatic flow under different experimentally-motivated parametric scenarios. / Tithof, Jeffrey; Boster, Kimberly A.S.; Bork, Peter A.R.; Nedergaard, Maiken; Thomas, John H.; Kelley, Douglas H.

In: iScience, Vol. 25, No. 5, 104258, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Tithof, J, Boster, KAS, Bork, PAR, Nedergaard, M, Thomas, JH & Kelley, DH 2022, 'A network model of glymphatic flow under different experimentally-motivated parametric scenarios', iScience, vol. 25, no. 5, 104258. https://doi.org/10.1016/j.isci.2022.104258

APA

Tithof, J., Boster, K. A. S., Bork, P. A. R., Nedergaard, M., Thomas, J. H., & Kelley, D. H. (2022). A network model of glymphatic flow under different experimentally-motivated parametric scenarios. iScience, 25(5), [104258]. https://doi.org/10.1016/j.isci.2022.104258

Vancouver

Tithof J, Boster KAS, Bork PAR, Nedergaard M, Thomas JH, Kelley DH. A network model of glymphatic flow under different experimentally-motivated parametric scenarios. iScience. 2022;25(5). 104258. https://doi.org/10.1016/j.isci.2022.104258

Author

Tithof, Jeffrey ; Boster, Kimberly A.S. ; Bork, Peter A.R. ; Nedergaard, Maiken ; Thomas, John H. ; Kelley, Douglas H. / A network model of glymphatic flow under different experimentally-motivated parametric scenarios. In: iScience. 2022 ; Vol. 25, No. 5.

Bibtex

@article{246070d9a5154a60a2ac0261aa9ced54,
title = "A network model of glymphatic flow under different experimentally-motivated parametric scenarios",
abstract = "Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain delivers nutrients, clears metabolic waste, and causes edema formation. Brain-wide imaging cannot resolve PVSs, and high-resolution methods cannot access deep tissue. However, theoretical models provide valuable insight. We model the CSF pathway as a network of hydraulic resistances, using published parameter values. A few parameters (permeability of PVSs and the parenchyma, and dimensions of PVSs and astrocyte endfoot gaps) have wide uncertainties, so we focus on the limits of their ranges by analyzing different parametric scenarios. We identify low-resistance PVSs and high-resistance parenchyma as the only scenario that satisfies three essential criteria: that the flow be driven by a small pressure drop, exhibit good CSF perfusion throughout the cortex, and exhibit a substantial increase in flow during sleep. Our results point to the most important parameters, such as astrocyte endfoot gap dimensions, to be measured in future experiments.",
keywords = "In silico biology, Neuroscience, Systems neuroscience",
author = "Jeffrey Tithof and Boster, {Kimberly A.S.} and Bork, {Peter A.R.} and Maiken Nedergaard and Thomas, {John H.} and Kelley, {Douglas H.}",
note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
doi = "10.1016/j.isci.2022.104258",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "5",

}

RIS

TY - JOUR

T1 - A network model of glymphatic flow under different experimentally-motivated parametric scenarios

AU - Tithof, Jeffrey

AU - Boster, Kimberly A.S.

AU - Bork, Peter A.R.

AU - Nedergaard, Maiken

AU - Thomas, John H.

AU - Kelley, Douglas H.

N1 - Publisher Copyright: © 2022 The Author(s)

PY - 2022

Y1 - 2022

N2 - Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain delivers nutrients, clears metabolic waste, and causes edema formation. Brain-wide imaging cannot resolve PVSs, and high-resolution methods cannot access deep tissue. However, theoretical models provide valuable insight. We model the CSF pathway as a network of hydraulic resistances, using published parameter values. A few parameters (permeability of PVSs and the parenchyma, and dimensions of PVSs and astrocyte endfoot gaps) have wide uncertainties, so we focus on the limits of their ranges by analyzing different parametric scenarios. We identify low-resistance PVSs and high-resistance parenchyma as the only scenario that satisfies three essential criteria: that the flow be driven by a small pressure drop, exhibit good CSF perfusion throughout the cortex, and exhibit a substantial increase in flow during sleep. Our results point to the most important parameters, such as astrocyte endfoot gap dimensions, to be measured in future experiments.

AB - Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain delivers nutrients, clears metabolic waste, and causes edema formation. Brain-wide imaging cannot resolve PVSs, and high-resolution methods cannot access deep tissue. However, theoretical models provide valuable insight. We model the CSF pathway as a network of hydraulic resistances, using published parameter values. A few parameters (permeability of PVSs and the parenchyma, and dimensions of PVSs and astrocyte endfoot gaps) have wide uncertainties, so we focus on the limits of their ranges by analyzing different parametric scenarios. We identify low-resistance PVSs and high-resistance parenchyma as the only scenario that satisfies three essential criteria: that the flow be driven by a small pressure drop, exhibit good CSF perfusion throughout the cortex, and exhibit a substantial increase in flow during sleep. Our results point to the most important parameters, such as astrocyte endfoot gap dimensions, to be measured in future experiments.

KW - In silico biology

KW - Neuroscience

KW - Systems neuroscience

U2 - 10.1016/j.isci.2022.104258

DO - 10.1016/j.isci.2022.104258

M3 - Journal article

C2 - 35521514

AN - SCOPUS:85129214877

VL - 25

JO - iScience

JF - iScience

SN - 2589-0042

IS - 5

M1 - 104258

ER -

ID: 344722471