Functional hyperemia drives fluid exchange in the paravascular space

Abstract

The brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that fluid movement through the arterial paravascular space (PVS) promotes metabolite clearance. We performed simulations to understand how arterial pulsations and dilations, and brain deformability affect PVS fluid flow. In simulations with compliant brain tissue, arterial pulsations did not drive appreciable flows in the PVS. However, when the artery dilated as in functional hyperemia, there was a marked movement of fluid. Simulations suggest that functional hyperemia may also serve to increase fluid exchange between the PVS and the subarachnoid space. We measured blood vessels and brain tissue displacement simultaneously in awake, head-fixed mice using two-photon microscopy. Measurements show that brain deforms in response to fluid movement in PVS, as predicted by simulations. Our results show that the deformability of the brain tissue needs to be accounted for when studying fluid flow and metabolite transport.

Bulk flow of cerebrospinal fluid observed in periarterial spaces is not an artifact of injection

“…Probability density functions show that the delay times between the peaks in the cardiac cycle and the peaks in V rms are nearly identical for the two infusion methods. While we can not rule out other physiological mechanisms that might drive CSF flow, such as functional hyperemia 35 or vasomotion 15,36 , we conclude that the currently employed methods of tracer infusion are not responsible for the observed flows.…”

nNOS-expressing interneurons control basal and behaviorally evoked arterial dilation in somatosensory cortex of mice

“…The pial arterioles are surrounded by CSF ( Abbott et al, 2018 ), whereas the penetrating arterioles are surrounded by a thin paravascular space ( Iliff et al, 2012 ) filled with collagen fibers tethering the artery to the brain ( Roggendorf and Cervós-Navarro, 1977 ). When the smooth muscle cells surround pial arteries relax, the vessel’s dilation need only displace CSF, which has viscosity near that of water, while dilation (or constriction) of penetrating arterioles must displace (or pull upon) the viscoelastic brain tissue ( Goriely et al, 2015 ; Weickenmeier et al, 2018a ; Weickenmeier et al, 2018b ; Kedarasetti et al, 2020 ). The viscoelasticity of brain tissue will function as an ultra-low-pass mechanical filter on diameter changes of penetrating arterioles, reducing the amplitude of ‘rapid’ dilations (on the order of seconds), although allowing slower dynamics (on the order of minutes), which could explain why we saw similar changes in both pial and penetrating arterioles baseline (which take place over minutes), but no effects on the ‘rapid’ locomotion-evoked dilations.…”

Neurovascular coupling and bilateral connectivity during NREM and REM sleep

“…On a more fundamental level, these results show that the vasodilation seen in the awake brain is smaller than the hemodynamic changes seen during sleep. This vasodilation during sleep may serve to circulate cerebrospinal fluid (Aldea et al, 2019;Fultz et al, 2019;Kedarasetti et al, 2020;van Veluw et al, 2020) or some other physiological role. (Drew et al, 2011;Huo et al, 2015a;Winder et al, 2017).…”