Abstract
The glymphatic system is a fluid-transport system that accesses all regions of the brain. It facilitates the exchange of cerebrospinal fluid and interstitial fluid and clears waste from the metabolically active brain. Astrocytic endfeet and their dense expression of the aquaporin-4 water channels promote fluid exchange between the perivascular spaces and the neuropil. Cerebrospinal and interstitial fluids are together transported back to the vascular compartment by meningeal and cervical lymphatic vessels. Multiple lines of work show that neurological diseases in general impair glymphatic fluid transport. Insofar as the glymphatic system plays a pseudo-lymphatic role in the central nervous system, it is poised to play a role in neuroinflammation. In this review, we discuss how the association of the glymphatic system with the meningeal lymphatic vessel calls for a renewal of established concepts on the CNS as an immune-privileged site. We also discuss potential approaches to target the glymphatic system to combat neuroinflammation.
Highlights
The blood–brain barrier (BBB) is a critical component of the central nervous system (CNS) that dampens environmental perturbations in interstitial ionic and chemical concentrations, and thereby supports the stability of synaptic transmission
This review focuses on the pivotal function of astrocytes in fluid transport and as global players for maintaining CNS homeostasis in the setting of either inflammatory processes in CNS or in systemic inflammation
(3) The third segment of the glymphatic system, which is common to the brain and eye, consists of perivenous efflux of interstitial fluid (ISF, dark blue arrows), which drains to the dural lymphatic vessels surrounding the brain and the optic nerve
Summary
The blood–brain barrier (BBB) is a critical component of the central nervous system (CNS) that dampens environmental perturbations in interstitial ionic and chemical concentrations, and thereby supports the stability of synaptic transmission. The CNS lacks a parenchymal lymphatic vessel system that supports fluid homeostasis and provides a path for immune surveillance in the peripheral organs. The lack of lymphatic vessels in the retina and brain presented a conceptual challenge in understanding how fluid homeostasis and the export of waste products are obtained within the confines of the CNS [1]. This review focuses on the pivotal function of astrocytes in fluid transport and as global players for maintaining CNS homeostasis in the setting of either inflammatory processes in CNS or in systemic inflammation. A few years after the initial description of the brain glymphatic system, the research groups of Kipnis and Alitalo independently discovered a lymphatic vessel network in the cerebral meninges. The meningeal lymphatic system serves traditional functions such as immune-cell trafficking and clearance of macromolecules from the brain [15,16]. We discuss how recent discoveries call for a revision of the classic concept of CNS immune privilege and how peripheral inflammation may propagate to induce neuroinflammation
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