Pulsatile flow drivers in brain parenchyma and perivascular spaces: a resistance network model study

Abstract

BackgroundIn animal models, dissolved compounds in the subarachnoid space and parenchyma have been found to preferentially transport through the cortex perivascular spaces (PVS) but the transport phenomena involved are unclear.MethodsIn this study two hydraulic network models were used to predict fluid motion produced by blood vessel pulsations and estimate the contribution made to solute transport in PVS and parenchyma. The effect of varying pulse amplitude and timing, PVS dimensions, and tissue hydraulic conductivity on fluid motion was investigated.ResultsPeriodic vessel pulses resulted in oscillatory fluid motion in PVS and parenchyma but no net flow over time. For baseline parameters, PVS and parenchyma peak fluid velocity was on the order of 10 μm/s and 1 nm/s, with corresponding Peclet numbers below 103 and 10−1 respectively. Peak fluid velocity in the PVS and parenchyma tended to increase with increasing pulse amplitude and vessel size, and exhibited asymptotic relationships with hydraulic conductivity.ConclusionsSolute transport in parenchyma was predicted to be diffusion dominated, with a negligible contribution from convection. In the PVS, dispersion due to oscillating flow likely plays a significant role in PVS rapid transport observed in previous in vivo experiments. This dispersive effect could be more significant than convective solute transport from net flow that may exist in PVS and should be studied further.

Intracranial pressure elevation alters CSF clearance pathways

“…Our model did not include the effect of cardiac or respiratory pulsatility neither in the arterial, venous or CSF compartments, which all has been proposed to drive glymphatic clearance [31,46,5]. In particular, the cardiac pulsation on the arterial side seems related to the PVS pulsatile movement as shown in Mestre et al [46], but modeling attempts deem it unlikely that arterial wall movements alone drive a net flow of sufficient magnitude for clearance of fluid [3,54].…”

“…Furthermore, it has been argued that fixation, which was used by Bedussi et al [5], shrinks the PVS [46]. As such, the resistance of the PVS at the capillary level should be further investigated and compared to the high resistance to flow through the ECS of the brain parenchyma [29,62,54].…”

Adaptable pulsatile flow generated by quantitative imaging of stem-cell derived cardiomyocytes for disease modeling

“…The microenvironment of blood vessels in vivo includes constant exposure to shear stress from blood flow, which plays an important role in vascular formation and in maintaining vascular function 1, 2 . Pulsatile flow is generated by the periodic contraction of the left ventricle and maintained throughout the arteries, as well as in selected areas of veins and capillaries 3 . Blood flow is tightly correlated to ventricular contractility 4 , so abnormal heart rhythm impacts peripheral blood flow pattern 5 .…”

Glymphatic Optimal Mass Transport with Lagrangian Workflow Reveals Advective and Diffusion Driven Solute Transport

“…Recently, various computational analyses and simulations have been performed to better understand the driving mechanisms of transport across PVS boundaries and through ISF space [22][23][24] . Conservation principles are typically used to derive these simulations, a popular one being the porous media model [25][26][27] . Ray et al 26 proposed adding an advection term of this form to the (diffusive) porous media model and their simulations indicated the presence of advective transport in the ISF.…”

“…Conservation principles are typically used to derive these simulations, a popular one being the porous media model [25][26][27] . Ray et al 26 proposed adding an advection term of this form to the (diffusive) porous media model and their simulations indicated the presence of advective transport in the ISF. Simulations are very effective for distinguishing between advection and diffusion, but when applied in vivo, inferable insight becomes limited.…”