Time-dependent sleep disruption at simulated 7000 m in rats: Delineating the compensation-to-decompensation transition.

High-altitude exposure disrupts sleep, but the temporal dynamics remain poorly defined. This study characterises time‑dependent changes in sleep architecture, HPA axis function, inflammation, and central sleep‑regulatory molecules during subacute hypobaric hypoxia. Male Sprague‑Dawley rats were exposed to simulated 7000 m for 1, 3, 5, or 7 days (H1d-H7d). Sleep was recorded by wireless EEG/EMG. HPA axis hormones, inflammatory cytokines, and sleep‑regulatory molecules were measured in serum, hippocampus, and hypothalamus. Multi‑dimensional integration was performed using principal component analysis (PCA). Hypoxia progressively reduced total sleep time and sleep efficiency, increased REM sleep percentage, and fragmented wakefulness, accompanied by declines in SWS delta power and REM theta power. The HPA axis exhibited peripheral-central dissociation: serum ACTH increased, whereas hippocampal ACTH and CORT were suppressed. Peripheral inflammation followed a time‑dependent pattern: an early IL‑6 surge (H1d), sustained Th1 suppression (IL‑12), and delayed IL‑10 elevation (H7d). Hippocampal BDNF, GABA, and histamine progressively declined; hypothalamic PGD₂, orexin A, 5‑HT, and histamine similarly decreased, while dopamine increased at H5d-H7d. PCA indicated a temporal separation between H3d and H5d, suggesting a transition from compensation to decompensation (mean Q² = 0.43). Subacute hypobaric hypoxia is associated with a time‑dependent transition from compensation to decompensation, characterised by sleep architecture collapse, HPA axis uncoupling, phased inflammation, and progressive loss of central sleep‑regulatory molecules. These findings offer a descriptive framework for understanding high‑altitude sleep disorders.