Brain Lymphatic Drainage: Emerging Concepts and Current Perspectives - A Comprehensive Review

Abstract

The central nervous system (CNS) has long been considered devoid of a classical lymphatic system, leading to the long-held concept of immune privilege. However, recent, paradigm-shifting discoveries have unequivocally demonstrated the existence of functional lymphatic vessels in the meninges of the brain. These meningeal lymphatic vessels (mLVs), in conjunction with the functionally defined glymphatic system (GS), form a comprehensive fluid clearance network crucial for maintaining brain homeostasis. This network facilitates the efficient bulk flow of cerebrospinal fluid (CSF) and interstitial fluid (ISF), clearing metabolic waste products such as amyloid-beta (Aβ) and α-synuclein, and orchestrating immune cell trafficking. Dysfunction within this complex drainage system is now strongly implicated in the pathogenesis of various neurological disorders, including Alzheimer’s disease, Parkinson’s disease, stroke, and hydrocephalus. This review consolidates historical perspectives, recent experimental and human imaging findings, and clinical implications, highlighting the transformative understanding of brain lymphatic drainage in both physiology and pathology, and identifying novel therapeutic targets.

Keywords: Meningeal lymphatics, Glymphatic system, Cerebrospinal fluid, Neurodegeneration, Brain drainage, AQP4, VEGFR3, Neuroinflammation.