The Glymphatic System: A Beginner's Guide

Neurochem Res. 2015 Dec;40(12):2583-99. doi: 10.1007/s11064-015-1581-6. Epub 2015 May 7.


The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system. Besides waste elimination, the glymphatic system also facilitates brain-wide distribution of several compounds, including glucose, lipids, amino acids, growth factors, and neuromodulators. Intriguingly, the glymphatic system function mainly during sleep and is largely disengaged during wakefulness. The biological need for sleep across all species may therefore reflect that the brain must enter a state of activity that enables elimination of potentially neurotoxic waste products, including β-amyloid. Since the concept of the glymphatic system is relatively new, we will here review its basic structural elements, organization, regulation, and functions. We will also discuss recent studies indicating that glymphatic function is suppressed in various diseases and that failure of glymphatic function in turn might contribute to pathology in neurodegenerative disorders, traumatic brain injury and stroke.

Keywords: Aging; Astrocytes; Cerebrospinal fluid secretion; Neurodegenerative diseases; Perivascular spaces; Sleep; The glymphatic system; Traumatic brain injury; Virchow–Robin spaces.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / cerebrospinal fluid
  • Animals
  • Astrocytes / metabolism*
  • Brain Injuries / cerebrospinal fluid
  • Cerebrospinal Fluid / metabolism
  • Cerebrospinal Fluid / physiology*
  • Humans
  • Lymphatic System / metabolism*