Arterial vasodilation drives convective fluid flow in the brain: a poroelastic model

The movement of fluid into, through, and out of the brain plays an important role in clearing metabolic waste. However, there is controversy regarding the mechanisms driving fluid movement, and whether the movement metabolic waste is primarily driven by diffusion or convection. The dilation of penetrating arterioles in the brain in response to increases in neural activity (neurovascular coupling) is an attractive candidate for driving fluid circulation, as it drives deformation of the brain tissue and of the paravascular space around arteries, resulting in fluid movement. We simulated the effects of vasodilation on fluid movement into and out of the brain using a novel poroelastic model of brain tissue. We found that arteriolar dilations could drive convective flow through the brain radially outward from the arteriole, and that this flow is sensitive to the dynamics of the dilation. Simulations of sleep-like conditions, with larger vasodilations and increased extracellular volume in the brain showed enhanced movement of fluid from the paravascular space into the brain. Our simulations suggest that both sensory-evoked and sleep-related arteriolar dilations can drive convective flow of cerebrospinal fluid from the paravascular space into the brain tissue around arterioles.

Functional hyperemia drives fluid exchange in the paravascular space

The brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that directional fluid movement through the arteriolar paravascular space (PVS) promotes metabolite clearance. We performed simulations to examine if arteriolar pulsations and dilations can drive directional CSF flow in the PVS and found that arteriolar wall movements do not drive directional CSF flow. We propose an alternative method of metabolite clearance from the PVS, namely fluid exchange between the PVS and the subarachnoid space (SAS). In simulations with compliant brain tissue, arteriolar pulsations did not drive appreciable fluid exchange between the PVS and the SAS. However, when the arteriole dilated, as seen during functional hyperemia, there was a marked exchange of fluid. Simulations suggest that functional hyperemia may serve to increase metabolite clearance from the PVS. We measured blood vessels and brain tissue displacement simultaneously in awake, head-fixed mice using two-photon microscopy. These measurements showed that brain deforms in response to pressure changes in PVS, consistent with our simulations. Our results show that the deformability of the brain tissue needs to be accounted for when studying fluid flow and metabolite transport.Acknowledgements: This work was supported by NSF Grant CBET 1705854.

Functional hyperemia drives fluid exchange in the paravascular space

The brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that fluid movement through the arteriolar paravascular space (PVS) promotes metabolite clearance. We performed simulations to understand how arteriolar pulsations and dilations, and brain deformability affect PVS fluid flow. In simulations with compliant brain tissue, arteriolar pulsations did not drive appreciable flows in the PVS. However, when the arteriole 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. These measurements showed that brain deforms in response to pressure changes 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.Acknowledgements: This work was supported by NSF Grant CBET 1705854.

Functional hyperemia drives fluid exchange in the paravascular space

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.

Functional hyperemia drives fluid exchange in the paravascular space

Maintaining the ionic and chemical composition of the extracellular spaces in the brain is extremely important for its health and function. However, the brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that the fluid movement through the paravascular space (PVS) surrounding penetrating arteries can help remove metabolites from the brain. The dynamics of fluid movement in the PVS and its interaction with arterial dilation and brain mechanics are not well understood. Here, we performed simulations to understand how arterial pulsations and dilations interact with brain deformability to drive fluid flow in the PVS. In simulations with compliant brain tissue, arterial pulsations did not drive appreciable flows in the PVS. In contrast, when the artery dilated with dynamics like those seen during functional hyperemia, there was a marked movement of fluid through the PVS. Our simulations suggest that in addition to its other purposes, functional hyperemia may serve to increase fluid exchange between the PVS and the subarachnoid space, improving the clearance of metabolic waste. We measured displacement of the blood vessels and the brain tissue simultaneously in awake, head-fixed mice using two-photon microscopy. Our measurements show that brain tissue can deform in response to fluid movement in the PVS, as predicted by simulations. The results from our simulations and experiments show that the deformability of the soft brain tissue needs to be accounted for when studying fluid flow and metabolite transport in the brain.