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Differential responses in the lungs of newborn mouse pups exposed to 85% or >95% oxygen
Lynette K Rogers1, Trent E Tipple, Leif D Nelin
1The Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, Ohio State University, Columbus, Ohio 43205, USA. rogersl@ccri.net
Insights
Different oxygen levels impact premature infant lung injury models. Higher oxygen (>95%) caused greater inflammation and developmental deficits in newborn mice compared to 85% oxygen exposure.
Area of Science:
- Neonatal physiology
- Pulmonary medicine
- Toxicology
Background:
- Premature infants face respiratory failure and hyperoxic lung injury, impacting lung development.
- Hyperoxia can cause lung inflammation and alter lung development in immature systems.
Purpose of the Study:
- To investigate differences in lung injury progression between newborn mice exposed to 85% and >95% oxygen.
- To establish models for studying differential effects of oxidation and inflammation in hyperoxic lung injury.
Main Methods:
- Newborn mice were exposed to either 85% or >95% oxygen.
- Evaluated weight gain, lung alveolarization, neutrophil counts, and levels of phospholipase A2, cyclooxygenase-2, and lipoxygenase.
- Measured prostaglandin levels (D2, E2, F2alpha) in lung tissues.
Main Results:
- Significant differences in weight gain and lung alveolarization were observed by day 14 between the 85% and >95% O2 groups.
- Neutrophil-driven inflammation was present in both groups by day 3, but markedly higher in the >95% O2 group by day 14.
- Prostaglandins D2, E2, and F2alpha were elevated in the >95% O2 group by day 7, indicating differential cyclooxygenase-2 product expression.
Conclusions:
- Exposure to >95% oxygen results in more severe lung injury, inflammation, and developmental deficits compared to 85% oxygen in newborn mice.
- The distinct responses suggest that different oxygen concentrations create unique models for studying hyperoxic lung injury mechanisms.
- Findings provide insights into the differential effects of oxidation and inflammation in immature lung development under hyperoxia.
Abstract:
Premature infants often develop serious clinical complications associated with respiratory failure and hyperoxic lung injury that includes lung inflammation and alterations in lung development. The goal of these studies is to test the hypothesis that there are differences in the course of lung injury in newborn mice exposed to 85% or >95% oxygen that provide models to address the differential effects of oxidation and inflammation. Our results indicate differences between the 85% and >95% O2 exposure groups by day 14 in weight gain and lung alveolarization. Inflammation, assessed by neutrophil counts, was observed in both hyperoxia groups by day 3 but was dramatically greater in the >95% O2-exposed groups by day 14 and associated with greater developmental deficits. Cytoplasmic phospholipase A2, cyclooxygenase-2, and 5-lipoxygenase levels were elevated but no patterns of differences were observed between exposure groups. Prostaglandins D2, E2, and F2alpha were increased in the tissues from mouse pups exposed to >95% O2 at 7 d indicating a differential expression of cyclooxygenase-2 products. Our data indicate that there are differences in the models of 85% or >95% O2 exposure and these differences may provide mechanistic insights into hyperoxic lung injury in an immature system.