Pulsatile flow drivers in brain parenchyma and perivascular spaces: a resistance network model study
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luids and Barriers of the CNS Open Access
RESEARCH
Pulsatile flow drivers in brain parenchyma and perivascular spaces: a resistance network model study Julian Rey and Malisa Sarntinoranont*
Abstract Background: In 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. Methods: In 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. Results: Periodic 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. Conclusions: Solute 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. Keywords: Rat cerebral cortex, Biotransport, Glymphatic theory, Extracellular flow, Bulk flow, Interstitial flow, Lumped parameter, Porous media, Cerebrospinal fluid, Fluid mechanics, Diffusion Background Since the 1970s the perivascular spaces (PVS) surrounding blood vessels have been thought to play a role in solute transport through brain tissue, specifically as conduits for rapid transport [1, 2]. The PVS are extracellular spaces formed by cylindrical arrangements of glial cells that surround intracortical arterioles and veins [3]. Rennels et al. [2] and more recently Iliff et al. [4] found that tracers injected into the subarachnoid space (SAS) of animal models were preferentially transported through the PVS of intracortical arteries at rates faster than would *Correspondence: [email protected] Department of Mechanical and Aerospace Engineering, University of Florida, PO Box 116250, Gainesville, FL 32611, USA
be expected from diffusion alone. In these studies, tracer moved in the direction of blood flow. Ichimura et al. [5] injected fluorescently labeled albumin into cortical perivascular spaces of rats with an open cranial window preparation and using video-densitometric measurements described slow oscillatory tracer motion within the PVS that was not biased in either direction. Carare et al. [6] and more recently Morris et al. [7] observed tracers injected into the paren
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