Meningeal Lymphatics: A Review and Future Directions From a Clinical Perspective

Korri S Hershenhouse, Orr Shauly, Daniel J Gould, Ketan M Patel, Korri S Hershenhouse, Orr Shauly, Daniel J Gould, Ketan M Patel

Abstract

The recent discovery of lymphatic vessels in the meningeal layers calls into question the known mechanisms of fluid and macromolecule homeostasis and immunoregulation within the central nervous system. These meningeal lymphatic vessels and their potential role in the pathophysiology of neurological disease have become a rapidly expanding area of research, with the hopes that they may provide a novel therapeutic target in the treatment of many devastating conditions. This article reviews the current state of knowledge surrounding the anatomical structure of the vessels, their functions in fluid and solute transport and immune surveillance, as well as their studied developmental biology, relationship with the novel hypothesized "glymphatic" system, and implications in neurodegenerative disease in animal models. Furthermore, this review summarizes findings from the human studies conducted thus far regarding the presence, anatomy, and drainage patterns of meningeal lymphatic vessels and discusses, from a clinical perspective, advancements in both imaging technologies and interventional methodologies used to access ultrafine peripheral lymphatic vessels.

Keywords: Alzheimer; multiple sclerosis; neurodegeneration; neurodegenerative; neuroimmunology.

Conflict of interest statement

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

© The Author(s) 2019.

Figures

Figure 1.
Figure 1.
The drainage pathway of interstitial fluid from the brain parenchyma to the meningeal lymphatic system. The glymphatic system regulates the flux of interstitial fluid from the brain parenchyma into perivascular spaces, continuous with the CSF containing subarachnoid space. CSF containing interstitial fluid is absorbed into meningeal lymphatic vessels associated with dural blood vessels. CSF indicates cerebrospinal fluid.
Figure 2.
Figure 2.
A schematic of human meningeal lymphatic vessels, adapted from skull-stripped subtraction T1-black-blood imaging. Source: Reprinted from Absinta et al.

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