Effects of Spaceflight Stressors on Brain Volume, Microstructure, and Intracranial Fluid Distribution

Astronauts are exposed to elevated CO₂ levels onboard the International Space Station. Here, we investigated structural brain changes in 11 participants following 30-days of head-down tilt bed rest (HDBR) combined with 0.5% ambient CO₂ (HDBR + CO₂) as a spaceflight analog. We contrasted brain changes observed in the HDBR + CO₂ group with those of a previous HDBR sample not exposed to elevated CO₂. Both groups exhibited a global upward shift of the brain and concomitant intracranial free water (FW) redistribution. Greater gray matter changes were seen in the HDBR + CO₂ group in some regions. The HDBR + CO₂ group showed significantly greater FW decrements in the posterior cerebellum and the cerebrum than the HDBR group. In comparison to the HDBR group, the HDBR + CO₂ group exhibited greater diffusivity increases. In half of the participants, the HDBR + CO₂ intervention resulted in signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), a constellation of ocular structural and functional changes seen in astronauts. We therefore conducted an exploratory comparison compared between subjects that did and did not develop SANS and found asymmetric lateral ventricle enlargement in the SANS group. These results enhance our understanding of the underlying mechanisms of spaceflight-induced brain changes, which is critical for promoting astronaut health and performance.