Sleep deprivation and glymphatic system dysfunction as a risk factor for SANS during long-duration spaceflight

A unique constellation of ocular structural changes and visual anomalies known as Spaceflight Associated Neuro-ocular Syndrome (SANS) affects 70 % of crew members after long-duration spaceflight. Current hypotheses regarding the etiology of SANS discuss cephalad fluid shifts and venous congestion, which are correlated with elevated intra-cranial pressure (ICP) and enlarged perivascular spaces (PVS). These PVS comprise the glymphatic system (GS), a recently discovered network of influx and efflux pathways for cerebrospinal fluid (CSF) and metabolites in the central nervous system (CNS). Both glymphatic clearance and traditionally understood CSF circulation are affected by sleep-wake cycles, displaying a significant increase in fluid flow during sleep. Natural sleep has been associated with a 60 % increase in interstitial space in animal studies, which likely enhances GS exchange and outflow. Corresponding studies in humans using contrast-enhanced MRI associate sleep with greater glymphatic clearance compared to wakefulness. The sleep problems of astronauts during long-duration spaceflight have been well documented, ranging from sleep disruption and decreased quality to insufficient sleep duration. With recent terrestrial studies providing evidence that sleep deprivation impairs molecular clearance from the human brain, it follows that similar glymphatic dysfunction may arise due to these conditions in astronauts. Thus, in addition to impairing crew member work performance on long-duration space missions, sleep deprivation may exert long-term neuro-ocular effects via decreased glymphatic efficiency and clearance. The adverse impact of the resulting cognitive and visual disturbances presents a major future performance risk to astronauts. This work discusses the existing body of literature regarding the connections between circadian disruption and glymphatic disruption as a potential contributing mechanism for the development of SANS. This association should receive focused attention in future research as a potential risk factor for SANS. In addition, interventions that enhance extraterrestrial sleep quality and duration may prove to be practical countermeasures for the prevention of this syndrome.