Physiological cerebrospinal fluid interactions between brain and eye structures are altered after long‐duration spaceflight

Long-duration spaceflight represents an extreme challenge, triggering adaptive responses including spaceflight-associated neuro-ocular syndrome, characterized by diminished visual acuity and ocular changes, which is a significant health risk for Mars missions. Concurrently, spacefarers experience brain adaptations, including ventricular expansion and CSF redistribution; however, the integrative physiological mechanisms linking these brain-eye responses remain unestablished. We applied automated morphometric analysis to investigate brain-eye relationships using high-resolution MRI data from terrestrial control subjects and spacefarers, conducting correlation analysis between third ventricle volume and ocular parameters. Analysis revealed significant baseline correlations between third ventricle volume and multiple ocular parameters in healthy control subjects, including globe dimensions, optic nerve sheath volume, optic nerve length and retro-orbital width. Following spaceflight, adaptations occurred: optic nerve sheath volume increased by 11.93 ± 6.07 mm³ (right) and 27.22 ± 8.74 mm³ (left), and optic nerves lengthened by 0.38 mm (right) and 0.47 mm (left). The baseline analysis showed that multiple orbital structures were correlated with third ventricle volume, whereas longitudinal change analysis revealed selective associations: only globe changes were correlated with third ventricle expansion. This study demonstrates structure-specific brain-eye relationships consistent with CSF-mediated coupling as a mechanism underlying spaceflight-associated neuro-ocular syndrome during the cranial microgravity response. Following spaceflight, third ventricle expansion is correlated selectively with globe changes, while dissociating from optic nerve sheath and retro-orbital adaptations, providing quantitative evidence that microgravity creates differential biomechanical effects across orbital compartments. This supports CSF compartmentalization and the limited intracranial volume expansion (cranial ceiling effect) as underlying mechanisms. The findings illuminate the limits of brain elastic tissue expansion during intracranial fluid accumulation in astronauts.