Assessment of long-term functional outcomes in a murine model of bronchopulmonary dysplasia
Lumeng J Yu, Victoria Ko, Scott C Fligor, Savas T Tsikis, Amy Pan, Jordan D Secor, Duy T Dao, Lorenzo Anez-Bustillos, Bennet S Cho, and Mark Puder
Dept. of Surgery, Vascular Biology Program, Boston Children's Hospital, Boston, MA
Background: Bronchopulmonary dysplasia (BPD) affects up to 40% of infants born before 28 weeks’ gestation and is characterized by alveolar simplification. Many of these children will require surgical care. We assess a murine model of BPD for persistent long-term functional outcomes that may mirror those of human BPD. Methods: Newborn C57Bl/6J mouse littermates were exposed to normoxia (21% O2) or hyperoxia (75% O2) for 10 days. On postnatal day 10, one cohort underwent pulmonary function testing (PFT), followed by lung harvest for morphometric analysis. A second cohort of pups were recovered in normoxia until eight weeks of age for treadmill exercise tolerance testing (TETT), PFT, and lung morphometrics.
Results: Hyperoxia exposure significantly increased compliance and inspiratory capacity at postnatal day 10. On morphometrics, this correlated with increased mean linear intercept and significantly decreased alveolar count, both hallmarks of alveolar simplification. At postnatal week eight, mice exposed to hyperoxia in the neonatal period had persistently increased compliance and inspiratory capacity on PFT and alveolar simplification on morphometry. This correlated with significantly reduced running distance and time prior to exhaustion on TETT compared to normoxia controls.
Conclusion: Murine neonatal oxygen exposure provokes a reliable phenotype of BPD, with alveolar simplification on morphometric analysis, and functional deficits on PFT and TETT, which persist into adulthood. Application of this model and its long-term assessments will be crucial in evaluating potential treatments for BPD.
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