Effects of short-term simulated microgravity on changes in extracellular space structure and substance diffusion and clearance

Substance transportation and clearance in the brain extracellular space (ECS) is crucial to brain function, but simulated microgravity disrupts substance diffusion and clearance in the brain ECS and there is limited knowledge regarding these disruptions. This study employed a tracer-based magnetic resonance imaging (MRI) technique to examine the impact of simulated microgravity on hippocampal ECS structure and the drainage of brain interstitial fluid (ISF) in a tail-suspended hindlimb-unloading rat model. The results demonstrated that under simulated microgravity conditions for 3, 7, and 14 days, the volume fraction of the hippocampal ECS increased in hindlimb unloading rats, and short-term (3 days) simulated microgravity expedited the drainage of the hippocampal ISF, but the drainage slowed under longer (7 or 14 days) simulated microgravity. These findings suggested that simulated microgravity alters the structure of the brain ECS and the speed of brain ISF drainage, which may have implications for space-flight-related brain injuries and relevant neuroprotective approaches via the brain ECS.