Studies that provide mechanistic insights into the development of effective countermeasures for preventing bone and muscle deterioration during and after spaceflight; and
Use of ground-based model systems, such as hindlimb unloading in rodents, to investigate the mechanisms of changes that reproduce in-flight and postflight effects.
Mechanistic studies and exploitation of ground-based animal models are indeed being emphasized by NASA in both disciplines. The growing use of genetically modified mice (knockout and transgenic) is of particular interest and importance, although flight experiments will be required to validate mechanistic hypotheses so obtained. Caging for mice suitable for Shuttle and International Space Station (ISS) flight experiments is now available.
A third recommendation of the Strategy report, to investigate the relationship between exercise activity and protein-energy balance in flight, will ultimately require flight experiments. However, preliminary ground-based studies will be important antecedents to flight and have recently been started.
Two additional recommendations—to obtain a database on the course of spaceflight-related bone loss and its reversibility in humans, and to establish hormone profiles on humans before, during, and after spaceflight—cannot be addressed until appropriate flight opportunities return.
The three recommendations of the Strategy report for high-priority research in the areas of vestibular function, the vestibulo-ocular reflex, and sensorimotor integration all involved extensive studies in spaceflight. Preliminary investigations were carried out on Neurolab related to the recommendation for in-flight recordings of signal processing following otolith afferent stimulation. However, the highest-priority recommendation, to determine the basis for the compensatory mechanisms on Earth and in space and evaluate whether the mechanisms are the same, has not yet been addressed. Similarly, studies to determine the effects of microgravity on the adaptation of the vestibulo-oculomotor system to sensory perturbations will require spaceflight.
In a parallel section defining high priorities for research in fundamental gravitational biology, the Strategy report recommended functional magnetic resonance imaging (fMRI) studies on astronauts pre-and postflight to determine the effects of microgravity on neural space maps. Initiation of such studies must also await the availability of appropriate flight opportunities.
High-priority issues included determination of the mechanisms underlying inadequate total peripheral resistance during postflight orthostatic stress; extension of current knowledge of cardiovascular adjustments to long-duration exposure to microgravity; reevaluation and refinement of existing countermeasures; and development of methods for referencing intrathoracic vascular pressures to systemic pressures in microgravity. These studies also require flight opportunities. Although the ability to conduct experiments on the ISS will ultimately be required, much of the necessary knowledge could be obtained from short-term Shuttle-based flight and postflight studies.