The Lymphatic System of the Brain (Glymphatic and Meningeal Lymphatics): Implications for Waste Clearance and Immunosurveillance

Abstract

For decades, the brain was considered an immune-privileged organ lacking a traditional lymphatic system; however, the recent discoveries of the glymphatic pathway and meningeal lymphatic vessels have fundamentally reshaped our understanding of central nervous system (CNS) waste clearance and immune surveillance. This review aims to highlight the current state of knowledge on these systems, emphasizing their integrated role in neural health and disease. We first detail the anatomy and physiology of the glymphatic and meningeal lymphatic components, outlining their distinct and collaborative functions. We then explore the mechanisms of glymphatic solute transport and its regulation by factors such as sleep, respiration, and arterial pulsatility. The discussion extends to the structural organization and systemic connections of meningeal lymphatic vessels, highlighting their role in immune cell trafficking. A summary of advanced neuroimaging techniques, from magnetic resonance to optical methods, is provided to illustrate how these pathways can be visualized and assessed in vivo. Furthermore, we examine clinical evidence linking dysfunction in these clearance systems to neurodegenerative, cerebrovascular, and neuroinflammatory disorders. Finally, we survey emerging therapeutic strategies that target these pathways to enhance waste removal and modulate neuroimmunity. Future research should focus on elucidating the precise molecular crosstalk within this neuro-lymphatic interface and translating non-invasive modulation techniques into effective clinical interventions for a range of neurological conditions