A brain-wide model of glymphatic solute transport

Metabolic waste removal through fluid systems, such as the lymphatic system, is indispensable for maintaining homeostasis. The brain contains no lymph vessels, prompting research into alternative waste clearance methods. One hypothesis is of the glymphatic system, in which waste is cleared via cerebrospinal fluid (CSF) flowing through the perivascular spaces that surround blood vessels. CSF trickles through the outer wall of the perivascular space to clear waste from the brain. While several models and in vivo studies have explored CSF flow, there has been little investigation into the motion of waste within that fluid, particularly on the brain-wide scale. Many solutes are created and removed through cellular activity, creating sources and sinks in the fluid network. We build on an existing hydraulic resistance model of CSF flow through periarterial spaces and the parenchyma [1]. Using flow rates from the model, we solve two different 1D, steady-state advection-diffusion equations. In one equation, which is appropriate for the delivery of nutrients or drugs, the source term describing solute gain and loss depends on the concentration within the perivascular space. In the other, which is appropriate for wastes produced in the brain, the source term is independent of concentration. Some model parameters such as porosities and solute production rates are not well defined, so we perform a sensitivity analysis to determine in which areas of the model further in vivo investigation is needed to ensure accuracy.

[1] Tithof, Jeffrey, et al. "A network model of glymphatic flow under different experimentally-motivated parametric scenarios." Iscience 25.5 (2022): 104258.