How Do Meningeal Lymphatic Vessels Drain the CNS?

Abstract

The many interactions between the nervous and the immune systems, which are active in both physiological and pathological states, have recently become more clearly delineated with the discovery of a meningeal lymphatic system capable of carrying fluid, immune cells, and macromolecules from the central nervous system (CNS) to the draining deep cervical lymph nodes. However, the exact localization of the meningeal lymphatic vasculature and the path of drainage from the cerebrospinal fluid (CSF) to the lymphatics remain poorly understood. Here, we discuss the potential differences between peripheral and CNS lymphatic vessels and examine the purported mechanisms of CNS lymphatic drainage, along with how these may fit into established patterns of CSF flow.

Figure 1. Production and circulation of CSF within the CNS

Schematic representation of the pattern of intracranial CSF flow. A. CSF is produced by the choroid plexus of the lateral and fourth ventricles, and flows from the third ventricle to the fourth ventricle through the cerebral aqueduct. After circulating over the hemispheres, CSF absorption into the superior sagittal sinus, transverse sinus, and sigmoid sinuses is via arachnoid granulations, as well as efflux from the CNS along the olfactory nerves through the cribriform plate. B. Schematic representation of CSF-ISF flow from and to the subarachnoid space. CSF can diffuse in and out of the brain parenchyma along the perivascular space.

Figure 2. Possible localizations of CNS lymphatic vessels within the meninges

A. Lymphatic vessels are located within the dura layers in close apposition to the venous sinuses. B. Lymphatics are located at the interface between the dura and the arachnoid layers. C. Lymphatics are exposed to the subarachnoid space. Macromolecules (yellow) are seen within the subarachnoid space and within the lymphatic vessels into which they are draining.