Glymphatic System of the Brain: Anatomy, Physiology, and Clinical Implications

Cerebrospinal fluid (CSF) dynamics are increasingly recognized as central to brain waste clearance. Beyond the classical view of unidirectional CSF circulation, recent studies have identified the glymphatic system and meningeal lymphatic vessels as major complementary pathways. Glymphatic transport is driven by arterial pulsation, respiration, vasomotion, and strongly enhanced during slow-wave sleep. Advances in neuroimaging, including DTI-ALPS, EPVS quantification, contrast-enhanced magnetic resonance imaging (MRI), and ultrafast functional MRI, have enabled in vivo assessment of these mechanisms. Impaired glymphatic function has been linked to neurodegenerative and cerebrovascular diseases, highlighting its clinical relevance. Potential interventions range from lifestyle measures such as sleep optimization, exercise, and vascular risk control, to pharmacological and experimental strategies aiming to modulate CSF flow. These insights open new opportunities to target the glymphatic-lymphatic axis for the prevention and treatment of neurological disorders.