Abstract
AbstractClearance of protein waste products from the brain is accomplished by a combination of advection and diffusion in cerebrospinal fluid (CSF) and interstitial fluid (ISF). In the glymphatic model, there is a flow of ISF in the interstitial space, and both advection and diffusion occur there. Such a flow of ISF would be slow and difficult to detect directly, and its existence has proved controversial. Waste clearance has been shown to occur mainly during sleep, during which the volume of the interstitial space increases substantially due to ISF emitted from astrocytes. Here I show that this volume increase of the interstitial space, by itself, should lead to a slight reduction of diffusive transport, due to dilution of the waste solute, but to a significant increase in flow rate and advective transport, due to lowered hydraulic resistance. Thus, a flow of ISF together with the observed volume increase of the interstitial space might provide an important mechanism contributing to the enhanced clearance during sleep.
Funder
NIH/National Institute of Aging
U. S. Army Research Office
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Developmental Neuroscience,Neurology,General Medicine
Reference20 articles.
1. Iliff J, Wang M, Liao Y, Plogg B, Peng W, Gundersen G, Benveniste H, Vates G, Deane R, Goldman S, Nagelhus E, Nedergaard M. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid $$\beta$$. Sci Transl Med. 2012;4(147):147–51.
2. Mestre H, Mori Y, Nedergaard M. The brain’s glymphatic system: current controversies. Trends Neurosci. 2020. https://doi.org/10.1016/j.tins.2020.04.003.
3. Thomas JH. Fluid dynamics of cerebrospinal fluid flow in perivascular spaces. J R Soc Interface. 2019;16(1):52–7.
4. Rennels ML, Blaumanis OR, Grady PA. Rapid solute transport throughout the brain via paravascular fluid pathways. Adv Neurol. 1990;52:431.
5. Hannocks M-J, Pizzo ME, Huppert J, Deshpande T, Abbott NJ, Thorne RG, Sorokin L. Molecular characterization of perivascular drainage pathways in the murine brain. J Cereb Blood Flow Metab. 2018;38(4):669–86. https://doi.org/10.1177/0271678X17749689 (PMID: 29283289).
Cited by
15 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献