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Annu Rev Pathol. 2018 Jan 24;13:379-394. doi: 10.1146/annurev-pathol-051217-111018.

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.

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Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, New York 14642, USA; email: ,
Department of Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA.


The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.


amyloid-β; aquaporin-4; astrocyte; cerebrospinal fluid; glymphatic; perivascular space

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