Interestingly, exposure of rats to hypobaric hypoxia (10.8 % O2, at altitude of ~5000 m) for 2 days increased plasma levels of CRH, TNF-α, IL-1β (Fig. 1g–i), and hypoxia (7000 m, 8 h)-increased plasma levels of TNF-α and IL-1β were blocked by CRHR1 antagonist (CP154,526) (Fig. 1j, k), suggesting that hypobaric hypoxia induces an leave a blank spaceimmune-inflammatory response in humans and rats, which is positively associated with activation of CRH/CRHR1 and with the development of AMS in humans. This evidence concerns the gene CRHR1 and ablepharon macrostomia syndrome.