Evidence map›Paper›PMID 31217012›Full record

ArticleFluids and barriers of the CNS2019

Hydraulic resistance of periarterial spaces in the brain.

Jeffrey Tithof, Douglas H Kelley, Humberto Mestre, Maiken Nedergaard, John H Thomas

Abstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed.

  1. Vascular drivers of cerebrospinal fluid movement and enlarged perivascular spaces.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  2. High frame ratebioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Stretch and flow at the gliovascular interface: High-fidelity modeling of astrocyte endfeet.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Review
  7. Article
  8. Cerebral small vessel disease: The impact of glymphopathy and sleep disorders.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. A brain-wide solute transport model of the glymphatic system.Journal of the Royal Society, Interface · 2024
    Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Jeffrey TithofDepartment of Mechanical Engineering, University of Rochester, Rochester, NY, 14627, USA.
Douglas H KelleyDepartment of Mechanical Engineering, University of Rochester, Rochester, NY, 14627, USA.
Humberto MestreCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, 14642, USA.
Maiken NedergaardCenter for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, 14642, USA.
John H ThomasDepartment of Mechanical Engineering, University of Rochester, Rochester, NY, 14627, USA. thomas@me.rochester.edu.

Funding

Para-Vascular Basis of Small Vessel DiseaseR01NS100366 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2016 to 2020
$3.8M
Age and AD related bottlenecks in glymphatic-lymphatic waste transportRF1AG057575 · NIA · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN · 2017 to 2017
$3.2M
Capillary hyperemia in white matter: Novel mechanistic insight and effect of hypertension and agingRF1NS110049 · NINDS · UNIVERSITY OF ROCHESTER · PI NEDERGAARD, MAIKEN, WAN, JIANDI · 2018 to 2018
$2.9M
Glymphatic function in a transgenic rat model of Alzheimer's diseaseR01AG048769 · NIA · UNIVERSITY OF ROCHESTER · PI BENVENISTE, HELENE D, NEDERGAARD, MAIKEN · 2014 to 2018
$1.4M
NIA NIH HHS R01 AG048769NIA NIH HHS RF1 AG057575NIA NIH HHS RF1 AG057575-01NINDS NIH HHS R01 NS100366NINDS NIH HHS RF1 NS110049
6 · The paper itself

Abstract

backgroundPeriarterial spaces (PASs) are annular channels that surround arteries in the brain and contain cerebrospinal fluid (CSF): a flow of CSF in these channels is thought to be an important part of the brain's system for clearing metabolic wastes. In vivo observations reveal that they are not concentric, circular annuli, however: the outer boundaries are often oblate, and the arteries that form the inner boundaries are often offset from the central axis.

methodsWe model PAS cross-sections as circles surrounded by ellipses and vary the radii of the circles, major and minor axes of the ellipses, and two-dimensional eccentricities of the circles with respect to the ellipses. For each shape, we solve the governing Navier-Stokes equation to determine the velocity profile for steady laminar flow and then compute the corresponding hydraulic resistance.

resultsWe find that the observed shapes of PASs have lower hydraulic resistance than concentric, circular annuli of the same size, and therefore allow faster, more efficient flow of cerebrospinal fluid. We find that the minimum hydraulic resistance (and therefore maximum flow rate) for a given PAS cross-sectional area occurs when the ellipse is elongated and intersects the circle, dividing the PAS into two lobes, as is common around pial arteries. We also find that if both the inner and outer boundaries are nearly circular, the minimum hydraulic resistance occurs when the eccentricity is large, as is common around penetrating arteries.

conclusionsThe concentric circular annulus assumed in recent studies is not a good model of the shape of actual PASs observed in vivo, and it greatly overestimates the hydraulic resistance of the PAS. Our parameterization can be used to incorporate more realistic resistances into hydraulic network models of flow of cerebrospinal fluid in the brain. Our results demonstrate that actual shapes observed in vivo are nearly optimal, in the sense of offering the least hydraulic resistance. This optimization may well represent an evolutionary adaptation that maximizes clearance of metabolic waste from the brain.

Indexed as

Models, BiologicalBrainCerebral ArteriesCerebrospinal FluidGlymphatic SystemHumansPia MaterBulk flowCerebrospinal fluidFluid mechanicsGlymphatic systemHydraulic resistancePerivascular flow

Identifiers

PMID31217012
PMCPMC6585017

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.