Arterial Perivascular Space-Mediated Solute Transport in the Mouse Brain

The perivascular space (PVS) around cerebral arteries supports nutrient delivery and waste clearance, yet its transport mechanisms remain poorly defined. Here, we establish arterial PVS as a major solute transport route in the brain, exhibiting marked region-specific functionality. Using in vivo imaging, we show that solute movement within arterial PVS is not driven by cerebrospinal fluid (CSF) bulk flow, but follows bidirectional, arterial-pulsation-dependent dynamics. Parenchymal solutes diffuse into the vascular PVS network, where arterial pulsations propel them along perivascular pathways toward capillary and venous compartments to facilitate clearance. Notably, after cortical injection, reduced arterial pulsation and blood flow following carotid ligation significantly increased Aβ retention within arterial PVS. These results define a pulsation-driven perivascular transport system essential for brain solute clearance in health and disease.