Transport of interstitial fluid in the brain*

Accumulation of beta-amyloid protein in the vasculature of the brain is a characteristic of Alzheimer’s disease. One potential mechanism to clear beta-amyloid from the brain is via flow through perivascular spaces. Animal studies have shown that beta-amyloid carrying interstitial fluid is transported out of the brain through the perivascular space along artery walls. There is evidence that the direction of this flow is opposite to that of blood flow through the artery lumen. The perivascular space is mostly made up of layers of smooth muscles and it is assumed that the transport is driven by deformations of the artery wall. The origin of these deformations may be from heart pulsations or muscle cell contractions. We report on a hydrodynamic mechanism for reverse flow through the artery wall consisting of forward-propagating waves and their reflections. We have modeled the transport and identified a set of parameters to achieve a reverse flow. Measurements of arteries in the brains of anesthetized mice has been provided by Cornell University (N. Nishimura) using two-photon microscopy. Artery wall deformations from these measurements are used in our numerical simulations to predict interstitial fluid transport.