The glymphatic system: a new perspective on brain diseases

Abstract

The glymphatic system is a brain-wide perivascular pathway driven by aquaporin-4 on the endfeet of astrocytes, which can deliver nutrients and active substances to the brain parenchyma through periarterial cerebrospinal fluid (CSF) influx pathway and remove metabolic wastes through perivenous clearance routes. This paper summarizes the composition, overall fluid flow, solute transport, related diseases, affecting factors, and preclinical research methods of the glymphatic system. In doing so, we aim to provide direction and reference for more relevant researchers in the future.

Exploring neurodegenerative disorders using advanced magnetic resonance imaging of the glymphatic system

“…The glymphatic system plays a crucial role in maintaining the homeostasis of the neural microenvironment ( 1 ). It does so by facilitating the clearance of interstitial solutes, including for instance amyloid-beta and tau, two proteins considered pathophysiological hallmarks of Alzheimer’s disease (AD).…”

“…The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular channels formed by astroglial cells to promote the efficient elimination of soluble proteins and metabolites from the central nervous system ( 1 ). This system is a functional analog to the lymphatic system present in other organs.…”

“…The name “glymphatic” is a portmanteau of “glial” and “lymphatic” ( 2 ). The glymphatic system is active during sleep and primarily driven by arterial pulsation and the aquaporin-4 (AQP4) s maintains health by efficiently removing waste products and distributing essential nutrients ( 1 ). The significance of the glymphatic system is stressed by its association with several neurological disorders, including neurodegenerative disorders (NDs), traumatic brain injury, and stroke, among others ( 3 – 6 ).…”

“…This finding has also highlighted the importance of sleep for brain health, given that the glymphatic system is highly active during sleep ( 8 ). However, the physiological role of the glymphatic system is not limited to waste removal as it also plays a crucial role in distributing essential nutrients throughout the brain ( 1 ). These nutrients, including glucose, lipids, amino acids, and other molecules such as growth factors, are critical for maintaining brain health and physiological functioning ( 1 ).…”

“…However, the physiological role of the glymphatic system is not limited to waste removal as it also plays a crucial role in distributing essential nutrients throughout the brain ( 1 ). These nutrients, including glucose, lipids, amino acids, and other molecules such as growth factors, are critical for maintaining brain health and physiological functioning ( 1 ). The distribution of nutrients via the glymphatic system is particularly important given the brain’s high metabolic demands ( 9 ).…”