Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part I—Anatomy and Physiology

Normal physiologic function of organs requires a circulation of interstitial fluid to deliver nutrients and clear cellular waste products. Lymphatic vessels serve as collectors of this fluid in most organs; however, these vessels are absent in the central nervous system. How the central nervous system maintains tight control of extracellular conditions has been a fundamental question in neuroscience until recent discovery of the glial-lymphatic, or glymphatic, system was made this past decade. Networks of paravascular channels surrounding pial and parenchymal arteries and veins were found that extend into the walls of capillaries to allow fluid transport and exchange between the interstitial and cerebrospinal fluid spaces. The currently understood anatomy and physiology of the glymphatic system is reviewed, with the paravascular space presented as an intrinsic component of healthy pial and parenchymal cerebral blood vessels. Glymphatic system behavior in animal models of health and disease, and its enhanced function during sleep, are discussed. The evolving understanding of glymphatic system characteristics is then used to provide a current interpretation of its physiology that can be helpful for radiologists when interpreting neuroimaging investigations.