The head down tilt (HDT) position is commonly used to simulate vascular and tissue fluid dynamics during spaceflights. In HDT position, the cerebral autoregulation faces difficulties to adjust the vascular tone while the cephalad fluid shifts may yield increased intracranial pressures and altered mechanical properties. Recent MRI T2 mapping in HDT position have shown fluid overpressure in the brain and resulting loss of water contents in the CSF and orbital compartments. Brain MRE was performed here in similar HDT conditions. It was sensitive enough to provide new insights on the overall mechanical response of brain tissues in microgravity analogous conditions. Summary of Main Findings/Short Synopsis Brain fluid overpressure and resulting loss of water contents in CSF and orbital compartments were confirmed by T2 mapping in head down tilt position. The overall brain mechanical response in such microgravity analogous conditions, cerebral tissue stiffening, was revealed by whole brain MRE.