FIG. 7.

Theoretical multiorgan benefits of Hypothermia in a Syringe in the setting of long-duration spaceflight. Astronauts exposed chronically to microgravity and increased levels of radiation have evidence of cumulative tissue damage, and show marked changes in baseline physiology that may predispose organs such as the brain to a state of enhanced vulnerability. The utility of protective cooling in astronauts is a well-recognized potential therapy to prevent tissue damage during long-duration spaceflight. However, the technology involved in the implementation of cooling systems and protocols able to safely maintain a state of suspended animation in humans is incomplete. Moreover, adopting standard hypothermia equipment (e.g., the artic sun system) for a shuttle or medical module, and used for acute cooling in the event of an accidental injury (e.g., traumatic brain injury), will require overcoming design and training challenges to ensure patient safety in microgravity. Thus, in the relative near term, developing IV-based therapeutics that quickly and easily activate neuroprotective cold responsive signaling pathways in astronauts, and without the need for cooling, may represent a technically simpler approach for space travel (although not necessarily a replacement for the latter). Germane to that logic, key CSPs discussed in this review show promise in reversing physiological changes and cellular pathologies that appear to be associated with spaceflight. For instance, RBM3 (1) prevents cognitive impairment in models of Alzheimer's disease, (2) protects against muscle atrophy, and (3) may decrease bone loss. CIRBP promotes DNA repair mechanisms after ionizing radiation (but this effect is yet to be tested in neurons of the brain). Finally, RTN3 decreases Aβ plaque burden in the brain. CSHs may also mediate beneficial and/or detrimental effects on altered physiology in astronauts. In particular, Metrnl is associated with pathways involved in muscle strength and anti-inflammatory signaling in WAT. In addition, higher SHBG plasma levels are associated with increased white matter in men, but whether that relationship is causative or correlative remains unclear, and also needs to be investigated in women. Finally, FGF21 may activate neuroprotective pathways in the brain, or conversely, further promote a detrimental “space fever” phenotype in astronauts by activating heat-generating thermogenesis mechanisms in BAT. Aβ, beta-amyloid; IV, intravenous.