Lattice Boltzmann simulations reveal complementary function of different waste clearance mechanisms in the brain

Cellular byproducts in the brain are removed through two pathways: passage through the blood-brain barrier (BBB) to be swept away via blood flow or direct drainage into the cerebrospinal fluid (CSF) enveloping the brain. Arteries bifurcate into arterioles that extend into the parenchyma, ultimately branching into capillaries. Surrounding these vessels are perivascular spaces (PVSs), annular channels formed between the vessel wall and brain tissue. CSF enters the brain through perivascular routes, mixing with interstitial fluid to facilitate waste elimination via bulk flow. The alternative route involves the BBB, allowing waste to pass directly through vascular walls into the bloodstream. Both of these mechanisms are found within the brain vasculature and they provide redundancy for eliminating waste with different efficacy at high and low concentrations. In this study, we have developed a Lattice Boltzmann code to simulate the brain tissue including its arteries, veins, and capillaries, permitting the selective activation or deactivation of each pathway. We then compare the results with limited existing experimental data to compute critical parameters that have not yet been measured experimentally to unveil distinct functionalities in these two parallel outflow routes.