Utilization and Validation of Ground and Animal Models

The Strategy report repeatedly stressed the importance of validating and refining ground-based models. Current ground-based models can reproduce most of the symptoms of spaceflight, but there is not necessarily a commonality of mechanism. There is a critical unmet need for ongoing evaluation and refinement of existing models through comparison with flight data and endocrinological measurements, including a comprehensive in-flight human hormone profile.

When ground and flight studies have been compared, the results have sometimes been surprising. For example, a flight study on the Life and Microgravity Spacelab shuttle mission by Wronski et al. (1998) attempted to address the effects of glucocorticoids on rat bones during spaceflight, since there was ample ground-based data to suggest that glucocorticoids had a major role in bone loss. No effect of spaceflight or of cortisol on bone growth was found. Analysis of this unexpected finding showed that changes in bone in rats induced by spaceflight were influenced by (1) the way the animals were housed, (2) the age of the animal, (3) the particular strain (genetic background) of the rat used in the study, and (4) flight duration. Group housing inhibited bone formation, whereas single housing did not. Instead of being simple, the rat model turns out to be complex!

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