Brain cerebrospinal fluid flow.

Abstract

Cerebrospinal fluid flows around and into the brain, driven by intricate mechanisms, with profound implications for human health. According to the glymphatic hypothesis, in physiological conditions, cerebrospinal fluid flows primarily during sleep and serves to remove metabolic wastes like the amyloid-beta and tau proteins whose accumulation is believed to cause Alzheimer's disease. This paper reviews one research team's recent in vivo experiments and theoretical studies to better understand the fluid dynamics of brain cerebrospinal fluid flow. Driving mechanisms are considered, particularly arterial pulsation. Flow correlates closely with artery motion and changes when artery motion is manipulated. Though there are discrepancies between in vivo observations and predictions from simulations and theoretical studies of the mechanism, realistic boundary conditions bring closer agreement. Vessel shapes are considered, and have elongation that minimizes their hydraulic resistance, perhaps through evolutionary optimization. The pathological condition of stroke is considered. Much tissue damage after stroke is caused by swelling, and there is now strong evidence that early swelling is caused not by fluid from blood, as is commonly thought, but by cerebrospinal fluid. Finally, drug delivery is considered, and demonstrations show the glymphatic system could quickly deliver drugs across the blood-brain barrier. The paper closes with a discussion of future opportunities in the fast-changing field of brain fluid dynamics.