Functional and Clinical Relevance of the Crosstalk between the Glymphatic System and the Lymphatic System

In this review, we describe the concept of the glymphatic system as a glial-dependent clearance pathway in the brain. The hypothesis of the glymphatic system function suggests that dural lymphatic vessels absorb the cerebrospinal fluid and brain interstitial fluid via the glymphatic system and transport fluid into deep cervical lymph nodes. We present the accumulated data of various studies confirming the possible interconnection among the brain interstitial fluid, cerebrospinal fluid, and the glymphatic system. Anatomical features are discussed here together with a possible variety of glymphatic system functions, including the removal of waste products, transport of substances, and immune function. The glymphatic system is hypothesized to be involved in pathogenesis of many diseases, including Alzheimer's disease, stroke, and Parkinson's disease. We also discuss the role of the glymphatic system in pathophysiology and the complications of brain tumors. Meningeal lymphatics is thoroughly analyzed as well. Finally, we propose new treatment approaches to brain tumors, Parkinson's disease, and stroke using cervical lymph nodes and backward fluid flow in the meningeal lymphatic vessels.