Adverse respiratory patterns in near-term spontaneously breathing newborn lambs with elevated airway liquid volumes at birth.

Introduction: Recent evidence indicates that respiratory distress (RD) in near-term infants is caused by elevated airway liquid (EL) volume at the beginning of air-breathing after birth. While the adverse effects EL volumes on newborn lung function are known, the effects on respiratory control and breathing patterns shortly after birth (<4 h) are unknown. We investigated the effects of EL volumes on cardiorespiratory function and breathing patterns in spontaneously breathing near-term newborn lambs in the first hours after birth. Methods: At 137-8 days gestation (2-3 days prior to delivery; term ∼147 days), sterile surgery was performed on fetal sheep (n = 17) to implant catheters and blood flow probes. At 140 days, lambs were delivered via caesarean section under spinal anaesthesia. Airway liquid volumes were adjusted to mimic the level expected following vaginal delivery (∼10 ml/kg; Controls; n = 7), or elective caesarean section (∼30 ml/kg; elevated airway liquid group; EL; n = 10). Spontaneous breathing and cardiorespiratory parameters were recorded over four hours after birth. Non-invasive respiratory support with supplemental oxygen was provided if required. Results: EL lambs required higher inspired oxygen levels (p = 0.0002), were less active (p = 0.026), fed less (p = 0.008) and had higher respiratory morbidity scores than Controls (p < 0.0001). EL lambs also displayed higher rates of breathing patterns associated with RD, such as expiratory braking and tachypnoea. These patterns were particularly evident in male EL lambs who displayed higher levels of severe respiratory morbidity (e.g., expiratory braking) than female EL lambs. Conclusion: The study demonstrates that EL volumes at birth trigger respiratory behaviour and breathing patterns that resemble clinically recognised features of RD in term infants.

Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice.

Apolipoprotein E ε4 allele (APOE4) is the predominant genetic risk factor for late-onset Alzheimer's disease (AD). APOE4 mouse models have provided advances in the understanding of disease pathogenesis, but unaccounted variables like rodent housing status may hinder translational outcomes. Non-sterile aspects like food and bedding can be major sources of changes in rodent microflora. Alterations in intestinal microbial ecology can cause mucosal barrier impairment and increase pro-inflammatory signals. The present study examined the role of sterile and non-sterile food and housing on redox indicators and the immune status of humanized-APOE4 knock-in mice (hAPOe4). hAPOE4 mice were housed under sterile conditions until 22 months of age, followed by the transfer of a cohort of mice to non-sterile housing for 2 months. At 24 months of age, the redox/immunologic status was evaluated by flow cytometry/ELISA. hAPOE4 females housed under non-sterile conditions exhibited: (1) higher neuronal and microglial oxygen radical production and (2) lower CD68+ microglia (brain) and CD8+ T cells (periphery) compared to sterile-housed mice. In contrast, hAPOE4 males in non-sterile housing exhibited: (1) higher MHCII+ microglia and CD11b+CD4+ T cells (brain) and (2) higher CD11b+CD4+ T cells and levels of lipopolysaccharide-binding protein and inflammatory cytokines in the periphery relative to sterile-housed mice. This study demonstrated that sterile vs. non-sterile housing conditions are associated with the activation of redox and immune responses in the brain and periphery in a sex-dependent manner. Therefore, housing status may contribute to variable outcomes in both the brain and periphery.