Glymphatics in neurovascular diseases

The glymphatic system is a brain-wide waste clearance mechanism that mimics lymphatic functions and facilitates the removal of amyloid aggregates. It is supposed to be essential for maintaining homeostasis within the central nervous system including nutrient delivery, waste removal, and consistency of the ionic microenvironment. While its dysfunction has been implicated in a variety of neurodegenerative disorders, its neurovascular implications are only slowly emerging. Driven by arterial pulsatility synchronized with the cardiac cycle, the system promotes cerebrospinal fluid (CSF) influx through perivascular spaces, modulated by aquaporin-4 channels in astrocytes. Waste-laden fluid then drains via perivenous spaces to meningeal lymphatics and cervical lymph nodes. Dysfunctions in this system have been implicated in neurovascular conditions, including subarachnoid hemorrhage, idiopathic intracranial hypertension, steno-occlusive disease, and arteriovenous shunting disorders. These diseases disrupt glymphatic flow through altered pulsatility, impaired CSF influx, aquaporin-4 malfunction, or venous hypertension. Such impairments lead to waste accumulation, contributing to progressive cognitive decline, which may be reversible with targeted interventions. This review underscores the role of the glymphatic system in neurovascular diseases and highlights potential endovascular avenues to mitigate cognitive impairment due to an impaired glymphatic system.