Alexandra Vallet

Vasomotion during sleep and transport in the brain

March 03, 2023
vasomotionsleepbrain clearancetransport modelingdispersion

How do specific vascular dynamics during sleep affect solute transport in the brain?

Thanks to amazing interdisciplinary team efforts, our paper is out in Nature communications !

Sleep has been shown to enhance brain clearance both in mice and humans, but the precise reason for this is unknown. The motion of vascular walls is suspected to be the main player here but so far, observations have been done mainly during non-natural sleep and at the surface of the brain only.

Thankfully, Laura has a gift for making mice sleep naturally under the microscope! The team of GliaLab recorded specific dynamics patterns for penetrating arterioles, up to 200 um under the surface of the brains of mice.

It appears that vasomotion depends on the sleep stage. In particular, large amplitude low-frequency oscillations occur during NREM sleep.

But why? Could this be useful for the clearance of the brain?

With the team of Kent Andre Mardal at the University of Oslo and Simula research laboratory, we performed numerical simulations of solute transport around an oscillating vessel.

a Illustration showing the model of the PVS (top), and representative vasomotion-driven CSF flow simulation (bottom). b–d Peak fluid velocity in penetrating arteriole PVS generated by VLF and LF oscillations during a sleep cycle as predicted by biomechanical modeling using three scenarios where we added a fixed volume to the PVS obstructing flow corresponding to 0, 25, and 50% of our measured PVS in quiet wakefulness. The black circle represents the median, whereas the shading represents the distribution of all modeled vessels (n = 16 vessels, 4 mice). The value of the median is also given in the lower right corner for each box. WBS wake before sleep; NREM non-rapid eye movement sleep; IS intermediate state sleep; REM rapid eye movement sleep; WAS wake after sleep; PVS perivascular space; VLF very low frequency; LF low frequency.
a Illustration showing the model of the PVS (top), and representative vasomotion-driven CSF flow simulation (bottom). b–d Peak fluid velocity in penetrating arteriole PVS generated by VLF and LF oscillations during a sleep cycle as predicted by biomechanical modeling using three scenarios where we added a fixed volume to the PVS obstructing flow corresponding to 0, 25, and 50% of our measured PVS in quiet wakefulness. The black circle represents the median, whereas the shading represents the distribution of all modeled vessels (n = 16 vessels, 4 mice). The value of the median is also given in the lower right corner for each box. WBS wake before sleep; NREM non-rapid eye movement sleep; IS intermediate state sleep; REM rapid eye movement sleep; WAS wake after sleep; PVS perivascular space; VLF very low frequency; LF low frequency.

We predict that slow oscillations of arterioles during NREM sleep enhance solute transport by 62% compared to transport by diffusion only for a 2000kDa solute. The physical phenomenon behind this is called dispersion effect. It is due to the deformation of the particle concentration profile following the deformation of the vessel which enhance mixing, even if there is no net flow !

In comparison, the slow oscillations during a quiet awake state are much less effective (transport enhancement by 30%).

Sleeping

Overall, our data add mechanistic insight into why brain clearance is more efficient during sleep. We hypothesize that the entire sleep cycle is required for efficient fluid exchange and solute transport. So, don’t forget to rest and sleep!