The second postnatal week of life in the rat represents a critical window of brainstemneurochemical development characterized by abrupt and in some cases transient changes inconstitutive neurochemical expression. We showed previously that neonatal sustained hypoxia(SH, 11% O 2 , 5 days) exposure specifically between postnatal (P) days 11-15 (encompassingthe critical window) alters brainstem neurochemical development and impairs the acute hypoxicventilatory response (HVR); these effects are associated with a high degree of mortality notseen in younger or older age groups exposed to SH, suggesting the critical window ofvulnerability may have similarities to SIDS. Here, we extend these findings to determine whetherearlier SH exposure between P9-13 days (a slightly earlier window than our previous studies)also impairs the HVR and whether it is associated with delayed arousal responses. NeonatalLewis rats were exposed to SH (9.5% O 2 , 24 h/day) from P9-13 days of age; whole-bodyplethysmography was performed the day after SH ended (P14 ) to assess the acute HVR, arousal response time to acute hypoxia, and subsequent mortality. Age-matched normoxic ratsserved as controls. SH Rats exhibited an impaired early phase of the hypoxic ventilatoryresponse (0.43 +/- 0.17 ml/g/min above baseline) compared to normoxic raised rats (0.95 +/-0.21 ml/g/min above baseline), which was associated with significant mortality (60%) within 5days post-SH. Rats who died following SH exhibited a delayed arousal time to acute hypoxia(32.4 +/- 1.7 seconds) compared to normoxic rats (22.2 +/- 5.8 seconds). The mean arousaltime of rats that survived the post-SH period (26.2 +/- 3.5 seconds) was similar to normoxic rats.These data are consistent with numerous SIDS features including evidence of exposure toprolonged hypoxia, impaired respiratory control, and delayed arousal responses to acutehypoxia associated with unexpected mortality during a critical window of development Funding: NIH-5R01HD111415 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Caruso et al. (Fri,) studied this question.