Abstract
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.
Highlights
The brain is surrounded by cerebrospinal fluid (CSF), and the movement of CSF can clear metabolites from the central nervous system (CNS) [1,2,3,4,5,6,7]
For all the fluid– structure interaction models, the percentage of paravascular space (PVS) fluid exchanged with the subarachnoid space (SAS) is the main metric for metabolite clearance
While there have been several models investigating the fluid mechanics in the PVS [13, 19, 28], to our knowledge, none of them considered the impact of the soft, deformable brain tissue on CSF flow in the PVS
Summary
The brain is surrounded by cerebrospinal fluid (CSF), and the movement of CSF can clear metabolites from the central nervous system (CNS) [1,2,3,4,5,6,7]. Recent work [16, 17] has suggested directional CSF movement along the paravascular space (PVS) around arterioles. The PVS is a fluidfilled region between the arteriolar smooth muscle and astrocyte endfeet, and is believed to be connected to the sub-arachnoid space (SAS). The bulk movement of CSF in the SAS is thought to be driven by heart beat-driven pulsations of arterioles, which pump CSF through the PVS of pial arteries (“peristaltic pumping”) [16, 18, 19], An important approach for understanding fluid movement in the brain and the PVS is simulation of fluid dynamics. Calculations based on fluid mechanics [13, 19, Kedarasetti et al Fluids Barriers CNS (2020) 17:52
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
