Considering that in microgravity, demineralization (calcium loss in particular) occurs with an average of 1-2 % every 30 days, astronauts on a trip to Mars could easily experience osteoporosis and break bones without the possibility of re-entry for physical rehabilitation. Starting with the research done since 2006 by the Microgymn group, this paper present investigations from the field of neurophysiologic applications for physical rehabilitation during long-duration Space travel in microgravity. Experiments in comparative states such as parabolic flight, Earth gravity, and neutral buoyancy are planned to test the exercises for physical rehabilitation. A strong degree of innovation is applied and a new approach is proposed that applies rehabilitation using comfortable, easy-to-use, and non-intrusive equipment based mostly on rehabilitative isometric exercise, without the use of machines. Specific checks are being developed to emphasize changes in the recognition of afferences by the sensory and motor cortex, also using quantitative EEG. Movement capacity is also being investigated. The findings will permit creating rehabilitation protocols that will be helpful for astronauts working in zero gravity conditions.