What Is the "Glymphatic System"?

Abstract

Although the glymphatic system hypothesis is highly popular, it also lacks certain details. In this paper, an attempt was made to present a more clearly defined hypothesis, which is consistent with the past experiment results. The new hypothesis consists of (1) water flux in the brain parenchyma, (2) water and solutes pathway of the perivascular space, and (3) maintenance of this pathway by the network of astrocytes.

Keywords: clearance; glymphatic system; neurofluids.

Fig. 1

This illustrates the concept of the original glymphatic system hypothesis by Iliff et al. Note that the direction of venous flow is inverted from the original paper, in order to be consistent with other figures in this paper.

Fig. 2

This shows the flux of water in the interstitial space in the brain parenchyma. Water comes out of the arterial side of the capillary into perivascular space driven by the hydrostatic pressure of the blood, and then moves into the interstitial space through the gaps of astrocyte foot processes. Water is absorbed at the venous side of the capillary, where hydrostatic pressure is lower. Driving force within the brain parenchyma is primarily the osmotic pressure gradient.

Fig. 3

This shows the flux of solutes. They are driven by the water flux shown in Fig. 2. Although not directly proven, the perivenous space is likely to be continuous with the dural lymphatic system (red circle).

Fig. 4

This shows the network of astrocytes, connected to each other with gap junctions at their foot processes. Combined with the AQP4 channels at the foot processes surrounding the perivascular space, the entire network may work as a conduit to distribute water from the capillary to various parts of the perivascular space. AQP4, aquaporin-4.