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The Glymphatic System: A Beginner’s Guide

Abstract

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.

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Acknowledgments

This study was supported by NIH (NINDS NS075177 and NS078304). We thank Gerry Dienel, Ben Kress, and Rashid Deane for comments on the manuscript and Takahiro Takano for illustrations.

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Nadia Aalling Jessen.

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Nadia Aalling Jessen, Anne Sofie Finmann Munk and Iben Lundgaard have contributed equally to the work.

Special Issue: In honor of Dr. Gerald Dienel.

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Jessen, N.A., Munk, A.S.F., Lundgaard, I. et al. The Glymphatic System: A Beginner’s Guide. Neurochem Res 40, 2583–2599 (2015). https://doi.org/10.1007/s11064-015-1581-6

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Keywords

  • The glymphatic system
  • Astrocytes
  • Perivascular spaces
  • Virchow–Robin spaces
  • Cerebrospinal fluid secretion
  • Sleep
  • Aging
  • Neurodegenerative diseases
  • Traumatic brain injury