Perivascular interactions and tissue properties modulate directional glymphatic transport in the brain

The glymphatic theory suggests a convective transport mechanism through brain tissue, which has significant implications for both brain waste clearance and drug delivery. However, the existence and driving mechanisms of directional convection from periarterial to perivenous spaces remain debated. Additionally, the role of brain tissue stiffness in parenchymal transport remains unclear, as experiments have reported varying trends in stiffness changes in cases of aging and neurodegenerative diseases. Previous mechanistic models often simplify or neglect perivenous spaces and venous deformation, raising questions about whether arterial vasomotion alone can effectively drive artery-to-vein transport. In this study, we propose a multiphysics model that incorporates the poroelastic nature of brain tissue, capturing the dynamic interactions between periarterial and perivenous spaces. Our results demonstrate that net glymphatic flow sweeps from periarterial space across parenchyma and is modulated by the periarterial-perivenous interactions, leading to higher pressure in periarterial space that drives unidirectional bulk transport from periarterial space to perivenous space. We also show that brain tissue stiffness presents a non-monotonic effect on both the glymphatic transport and its efficiency, with their respective peaks occurring at different stiffness values. Notably, the glymphatic convection rate peaks at physiologically relevant levels of brain stiffness. Furthermore, phase-delayed venous vasomotion is found to enhance glymphatic flow. These findings highlight the critical role of perivascular interactions and provide a framework for exploring brain fluid dynamics and potential therapeutic strategies for neurodegenerative diseases.