Sleep cycle-dependent vascular dynamics enhance perivascular cerebrospinal fluid flow and solute transport

Bojarskaite, Laura; Bjørnstad, Daniel M; Vallet, A.; Binder, Kristin M. Gullestad; Cunen, Céline; Kuchta, Miroslav; Mardal, Kent‐André; Enger, Rune

doi:10.1101/2022.07.14.500017

Cited by 12 publications

(23 citation statements)

References 30 publications

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“…CSF and glymphatic function change according to circadian rhythm and/or sleep in animal models. In particular, extracellular volume fraction, perivascular intake and interstitial clearance (15), lymphatic efflux (16), choroid plexus gene expression (65), AQP4 polarization and drainage to lymph nodes (66), perivascular pulsations (67) all display significant variations. In humans, much less is known about CSF flow and exchange.…”

Section: Discussionmentioning

confidence: 99%

Human brain solute transport quantified by glymphatic MRI-informed biophysics during sleep and sleep deprivation

Vinje¹,

Zapf

Ringstad

et al. 2023

Preprint

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Whether you are reading, running or sleeping, your brain and its fluid environment continuously interacts to distribute nutrients and clear metabolic waste. Yet, the precise mechanisms for solute transport within the human brain have remained hard to quantify using imaging techniques alone. From multi-modal human brain MRI data sets in sleeping and sleep-deprived subjects, we identify and quantify CSF tracer transport parameters using forward and inverse subject-specific computational modelling. Our findings support the notion that extracellular diffusion alone is not sufficient as a brain-wide tracer transport mechanism. Instead, we show that human MRI observations align well with transport by either substantially enhanced (3.5 times faster) extracellular diffusion in combination with local clearance rates corresponding to a tracer half-life of up to 5 hours, or by extracellular diffusion augmented by advection with brain-wide average flow speeds on the order of 1-9 micrometers/min. Reduced advection fully explains reduced tracer clearance after sleep-deprivation, supporting the role of sleep and sleep deprivation on human brain clearance.

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Section: Discussionmentioning

confidence: 99%

Human brain solute transport quantified by glymphatic MRI-informed biophysics during sleep and sleep deprivation

Vinje¹,

Zapf

Ringstad

et al. 2023

Preprint

Self Cite

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“…Although our ndings indicate that functions linked to brain activation during REM sleep occur at the expense of ventricular CSF ow, REM sleep might still play an integral role in waste clearance. During the transition between NREM and REM sleep in rodents, the in ux of blood into the brain 43 increases vascular diameter 44 and compresses the perivascular space through which CSF normally enters the brain 12 . This might restrict the entry of new CSF into the brain, and thereby account for the reduction in CSF ow outside the brain tissue in pigeons.…”

Section: Discussionmentioning

confidence: 99%

“…Several aspects of sleep's proposed role in clearing waste from the brain remain unresolved. Notably, it is unclear how CSF ow changes throughout the ventricular system and brain during REM sleep 6,[10][11][12] , a paradoxical state with wake-like brain activity, during which we experience our most vivid, bizarre, storylike, and emotional dreams 8 . It is also unknown whether waste removal mediated by CSF ow through the brain is a general function of sleep shared by mammalian and non-mammalian species.…”

Section: Introductionmentioning

confidence: 99%

Wide-spread brain activation and reduced CSF flow during avian REM sleep

Ungurean¹,

Behroozi

Boeger

et al. 2022

Preprint

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Mammalian sleep has been implicated in maintaining a healthy extracellular environment in the brain. During wakefulness, neuronal activity leads to the accumulation of toxic proteins implicated in Alzheimer’s disease. The glymphatic system is thought to clear these proteins by flushing cerebral spinal fluid (CSF) through the brain. In mice, this process occurs during non-rapid eye movement (NREM) sleep. And, in humans, increased ventricular CSF flow during NREM sleep, visualized using functional magnetic resonance imaging (fMRI), is also thought to be coupled to flow through the glymphatic system. But does waste clearance occur throughout sleep or is it specific to NREM sleep? Using fMRI of naturally sleeping pigeons, we show that REM sleep, a paradoxical state with wake-like brain activity, during which we experience our most vivid dreams, is accompanied in birds with the activation of brain regions involved in processing visual information, including optic flow during flight. We further demonstrate that, compared to NREM sleep, REM sleep is associated with a sharp drop in ventricular CSF flow. Consequently, functions linked to brain activation during REM sleep might come at the expense of waste clearance during NREM sleep.

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“…( 2) and ( 4) allow estimating the effect of alterations on the gap area fraction (and C M , L p ). Moreover, vessel diameters are highly dynamic and can dilate up to 30 to 40 % of the vessel diameter [45] which leads to mechanical deformation of the astrocyte endfoot sheath observed in-vivo [46].…”

Section: Discussionmentioning

confidence: 99%

Estimates for the astrocyte endfoot sheath permeability of the extra-cellular pathway

Koch

Vinje

Mardal

2022

Preprint

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Background: Astrocyte endfoot processes are believed to cover all micro-vessels in the brain cortex and may play a significant role in fluid and substance transport into and out of the brain parenchyma. Detailed fluid mechanical models of diffusive and advective transport in the brain are promising tools to investigate theories of transport. Methods: We derive theoretical estimates of astrocyte endfoot sheath permeability for advective and diffusive transport and its variation in microvascular networks from mouse brain cortex. The networks are based on recently published experimental data and generated endfoot patterns are based on Voronoi tessellations of the perivascular surface. We estimate corrections for projection errors in previously published data. Results: We provide functional relationships between vessel radius and resistance that can be directly used in flow and transport simulations. We estimate endfoot sheath filtration coefficients in the range LP= 0.2 x 10-10to 2.7 x 10-10m/(Pa s), diffusion membrane coefficients in the range CM= 500 to 6000 1/m, and gap area fractions in the range 0.2% to 0.6%. Conclusions: The astrocyte endfoot sheath surrounding microvessels forms a secondary barrier to extra-cellular transport, separating the extra-cellular space of the parenchyma and the perivascular space outside the endothelial layer. The filtration and membrane diffusion coefficients of the endfoot sheath are estimated to be an order of magnitude lower than the extra-cellular matrix while being two orders of magnitude higher than the vessel wall.

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Sleep cycle-dependent vascular dynamics enhance perivascular cerebrospinal fluid flow and solute transport

Cited by 12 publications

References 30 publications

Human brain solute transport quantified by glymphatic MRI-informed biophysics during sleep and sleep deprivation

Human brain solute transport quantified by glymphatic MRI-informed biophysics during sleep and sleep deprivation

Wide-spread brain activation and reduced CSF flow during avian REM sleep

Estimates for the astrocyte endfoot sheath permeability of the extra-cellular pathway

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