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advection, Alzheimer’s disease, amyloid, biophysics, blood brain barrier, bulk flow, cerebrospinal fluid, circulation, extracellular, hydraulic, intracranial pressure, perivascular pumping, permeability, pia mater, pulsation, subarachnoid space, Virchow-Robin space, waste.


In a previous paper the author presented details of a new mechanism for the perivascular pump driving glymphatic flow—the brain’s waste removal system. The goal was to capture the essence of complex three-dimensional anatomy and physiology of the brain in a reduced order geometric model. The complexity required to make the model even approximately brain-like tended to obscure the most basic features of the perivascular pump. Here a bare-bones, “simplissimo” model of the perivascular pump is presented. It highlights only the most essential features of the pump mechanism. It also reveals components of brain anatomy and physiology that are not strictly necessary to make the pump work. Interestingly, these unnecessary features include pulsatile motion of the vascular walls, pressures inside the arteries and veins within the Virchow-Robin space, differences in arterial and venous compliance, the tapering of vascular branches, and the details of vascular branching. Instead, the softness of surrounding brain tissue and the relative diameters of venous vs. arterial perivascular cuffs are critical. Wave-like deformations of the soft brain tissue can create time averaged positive pressure in periarterial spaces, greater than that in perivenous spaces, owing to differences between antegrade and retrograde resistance to axial fluid flow along the annular channels of Virchow-Robin spaces. This new mechanism is scale independent from mouse to man, and can work despite the widely differing pulse rates of small versus large animals.