Chronic Hypertension and the Brain’s Waste Drainage System

An important system for brain waste clearance comprises a series of interconnected fluid and tissue compartments: the cerebrospinal fluid compartment, the glymphatic system, and the dura with the meningeal lymphatic vasculature, which drains to the cervical lymphatics. Although exchanges between these compartments are increasingly well documented, the mechanisms underlying their crosstalk and especially the regulation of brain waste clearance efficiency-including the role of immune surveillance along this pathway-remain incompletely understood. This interconnected pathway, designated the glymphatic-meningeal-cervical-lymphatic axis, is critically dependent on the cerebral vasculature, both structurally and functionally. Yet given this intimate vascular dependence, the effects of chronic hypertension-one of the most prevalent chronic diseases worldwide-on the structural and functional integrity of this axis remain remarkably understudied. This review examines each component of this pathway in physiological sequence, evaluating the evidence for hypertension-related dysfunction at each node and identifying where critical gaps remain.