A clinical primer for the glymphatic system

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science.

Automated summary

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the central nervous system (CNS) has implications for various neurological diseases. The glymphatic system, supported by astrocytes, plays a crucial role in directing extracellular fluid and removing waste products in order to optimize neurological function. Dysfunction in this system has been linked to CNS aging, neurodegenerative diseases, CNS injuries, and normal pressure hydrocephalus. Understanding the pathophysiology of glymphatics could lead to new therapeutic approaches.