Cited by 149Cerebrospinal fluid and hydrocephalusSleep and Wakefulness ResearchTraumatic Brain Injury and Neurovascular Disturbances

Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport

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Bojarskaite, Laura, Vallet, Alexandra, Bjørnstad, Daniel M., Gullestad Binder, Kristin M., Cunen, Céline, Heuser, Kjell, Kuchta, Miroslav, Mardal, Kent-Andre +1 more·2023·Nature Communications

Abstract

Perivascular spaces are important highways for fluid and solute transport in the brain enabling efficient waste clearance during sleep. However, the underlying mechanisms augmenting perivascular flow in sleep are unknown. Using two-photon imaging of naturally sleeping male mice we demonstrate sleep cycle-dependent vascular dynamics of pial arteries and penetrating arterioles: slow, large-amplitude oscillations in NREM sleep, a vasodilation in REM sleep, and a vasoconstriction upon awakening at the end of a sleep cycle and microarousals in NREM and intermediate sleep. These vascular dynamics are mirrored by changes in the size of the perivascular spaces of the penetrating arterioles: slow fluctuations in NREM sleep, reduction in REM sleep and an enlargement upon awakening after REM sleep and during microarousals in NREM and intermediate sleep. By biomechanical modeling we demonstrate that these sleep cycle-dependent perivascular dynamics likely enhance fluid flow and solute transport in perivascular spaces to levels comparable to cardiac pulsation-driven oscillations.

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  • REM sleep is marked by a pronounced increase in brain blood volume.

    “In contrast, REM sleep was marked by a pronounced increase in BBV, originating in the posterior cortex and slowly propagating across the brain.”

    From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [30]

    The Results (‘Pial arteries display sleep-cycle dependent vascular dynamics’; page unavailable) report pronounced arterial dilation during REM sleep in male mice, supporting increased vascular volume as an inference. The paper measures vessel diameter in the somatosensory cortex, not brain-wide blood volume, and does not establish the citing sentence’s posterior-cortex origin or propagation across the brain. (LLM, conf=0.86)

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  • Infraslow vasomotion predominates during NREM sleep in the rodent brain.

    “infraslow vasomotion predominate during NREM sleep in the rodent brain31,47”
  • Most prior studies looking at vascular dynamics have used two-photon imaging in head-fixed mice.

    “Most prior studies looking at vascular dynamics have used two-photon imaging in head-fixed mice31,47,98”
  • Cerebrospinal fluid flow in perivascular spaces is driven forward by dynamic constriction and enlargement of the cerebral arteries, and thereby the perivascular space volume, rather than a steady perivascular space size.

    “The data so far indicates that CSF flow in the perivascular spaces (PVSs) is driven forward by dynamic constriction and enlargement of the cerebral arteries, and thereby the PVS volume, rather than a steady PVS size27–31.”

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Research works printed but not linked: 1

  1. [5]Iliff JJ A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β Sci. Transl. Med. 2012 4 147ra111 10.1126/scitranslmed.3003748 22896675 PMC3551275 · DOI · Paper page

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Authors
Bojarskaite, L., Vallet, A., Bjørnstad, D. M., Gullestad Binder, K. M., Cunen, C., Heuser, K., Kuchta, M., Mardal, K.-A., & Enger, R.
Affiliations
  • Oslo University Hospital (NO)
  • University of Oslo (NO)
  • Norwegian Computing Center (NO)
  • Simula Research Laboratory (NO)
Corresponding author
  • Bojarskaite, Laura
  • Enger, Rune
Venue
Nature Communications
Published
2023-02-20
Volume
14
Issue
1
Pages
953-953
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4321367779
Cited by
149
References
42
Citations by year
2026: 30 · 2025: 59 · 2024: 36 · 2023: 24
FWCI
18.07
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
  • Norges Forskningsråd (249988, 271555/F20, 302326, 300305, 301013, 303362)
  • Ministry of Health and Care Services | Helse Sør-Øst RHF (2016070)
  • Olav Thon Foundation, Letten Foundation, University of Oslo, UNINETT Sigma2 AS, grant NN9279K.
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
sleep cycles, vascular dynamics, perivascular spaces, cerebrospinal fluid flow, solute transport, NREM sleep, REM sleep, microarousals, pial arteries, penetrating arterioles, vasodilation, vasoconstriction, brain waste clearance, biomechanical modeling, two-photon imaging
MeSH terms
Sleep, Slow-Wave, Animals, Arteries, Male, Sleep, Sleep, REM, Vasodilation, Mice

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