Brain Lymphatic Dysfunction in Subarachnoid Hemorrhage: Pathophysiology and Clinical Implications.

Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating cerebrovascular disorder with high morbidity and mortality, despite advances in aneurysm securing and neurocritical care. Clinical outcomes are determined by early brain injury (EBI), delayed cerebral ischemia (DCI), hydrocephalus, and long-term cognitive impairment, extending beyond the traditional focus on large-vessel vasospasm alone. Emerging evidence identifies the dysfunction of the glymphatic system and meningeal lymphatic pathway, the brain's primary clearance pathways, as a central and unifying mechanism linking acute hemorrhagic injury to delayed and chronic neurological sequelae. Following SAH, acute intracranial pressure elevation, subarachnoid blood clot burden, loss of arterial pulsatility, venous congestion, astrocytic aquaporin-4 perivascular depolarization, and neuroinflammation converge to suppress cerebrospinal fluid-interstitial fluid exchange and outflow in glymphatic system and subsequent meningeal lymphatic drainage. Persistent clearance failure promotes the retention of blood breakdown products, inflammatory mediators, and metabolic waste, amplifying microvascular dysfunction, cortical spreading depolarizations, blood-brain barrier disruption, and secondary ischemic injury. Importantly, accumulating data highlight venous pathology and meningeal lymphatic impairment as critical, yet underappreciated, contributors to delayed injury and post-SAH hydrocephalus. In this review, we synthesize the current knowledge of the physiological organization of glymphatic and meningeal lymphatic systems, delineate the mechanistic and molecular drivers of their dysfunction after SAH, and discuss clinical implications for EBI, DCI, hydrocephalus, and long-term cognitive outcomes. We further outline future directions, including translational imaging, biomarker development, and therapeutic strategies targeting clearance pathways, to advance disease-modifying approaches in SAH.