Glymphatic dysfunction in intracranial hemorrhage and neurodegenerative disease

The glymphatic system in the central nervous system functions analogously to systemic lymphatics involved in waste clearance, fluid dynamics and homeostasis. The glymphatic system is postulated to play a crucial role in the clearance of blood breakdown products within the brain parenchyma after intracranial hemorrhage. This narrative, non-systematic review aims to address theories on glymphatic dysfunction in hemorrhagic and neurodegenerative disease states, reflecting on new avenues for future clinical research and emerging therapies. A narrative review of the current literature was conducted on PubMed, Scopus, and Google Scholar using keywords related to glymphatic physiology, pathophysiological changes, and neurodegeneration. A major limitation of our review is the literature’s predominant preclinical evidence, with limited human validation and no standardized clinical biomarkers of glymphatic function. Preclinical studies suggest that the propagation of the inflammatory response and the initiation of blood coagulation in cerebrospinal fluid (CSF) lead to fibrin and fibrinogen deposits along the perivascular space. This aggregation of blood breakdown products and fibrin deposits is thought to clog the CSF passageway and impair glymphatic function, further damaging the brain parenchyma during secondary injury. Similar pathological processes of glymphatic dysfunction have been uncovered in relation to traumatic brain injury (TBI) and neurodegenerative processes. Restoring and enhancing the physiological function of the glymphatic system may be possible through a myriad of pharmacological, mechanical and behavioral therapeutic strategies. Despite advances in preclinical models, further research is needed to translate our basic science understanding of glymphatic dysfunction in intracranial hemorrhage towards feasible and actionable interventions.