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Circulation of cerebrospinal fluid and interstitial fluid around the central nervous system and through the brain transports not only those water-like fluids but also any solutes they carry, including nutrients, drugs, and metabolic wastes. Passing through brain tissue primarily during sleep, this circulation has implications for neurodegenerative disorders including Alzheimer's disease, for tissue damage during stroke and cardiac arrest, and for flow-related disorders such as hydrocephalus and syringomyelia. Recent experimental results reveal several features of this flow, but other aspects are not fully understood, including its driving mechanisms. We review the experimental evidence and theoretical modeling of cerebrospinal fluid flow, including the roles of advection and diffusion in transporting solutes. We discuss both local, detailed fluid-dynamic models of specific components of the system and global hydraulic models of the overall network of flow paths.
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Supplemental Video 1: Micron-scale fluorescent tracer particles (green) injected at the back of the skull are swept along by flowing CSF (blue) and pass through the perivascular space surrounding a surface artery (red). Automated particle tracking measurements of their positions and velocities make it possible to overlay pathlines colored according to the instantaneous velocity of each. Though tracer particles do not enter penetrating PVSs, two-photon microscopy through a cranial window allows quantifying flows in surface PVSs with high fidelity and up to 30 min at a time. Imaging provided by Antonio Ladron-de-Guevara and Maiken Nedergaard.