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Refinement of the hyperoxia-based experimental mouse model of bronchopulmonary dysplasia

Claudio Nardiello, Ivana Mizíková, Jordi Ruiz-Camp, Werner Seeger, Rory Morty
European Respiratory Journal 2016 48: PA4027; DOI: 10.1183/13993003.congress-2016.PA4027
Claudio Nardiello
1Lung Development and Remodelling, Max Planck Institute, Bad Nauheim, Germany
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Ivana Mizíková
1Lung Development and Remodelling, Max Planck Institute, Bad Nauheim, Germany
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Jordi Ruiz-Camp
1Lung Development and Remodelling, Max Planck Institute, Bad Nauheim, Germany
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Werner Seeger
1Lung Development and Remodelling, Max Planck Institute, Bad Nauheim, Germany
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Rory Morty
1Lung Development and Remodelling, Max Planck Institute, Bad Nauheim, Germany
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Abstract

Bronchopulmonary dysplasia (BPD) is a complication of premature birth, characterized by arrested alveolarisation. Studies on BPD rely on hyperoxia-based rodent models, which lack standardisation.We aimed to assess the minimum exposure and concentration of O2 required for arrested alveolarisation. Newborn C57BL/6J mouse pups were exposed to 21%, 40%, 60% and 85% O2 for 14 days or to 85% O2 for 4 h, or 1, 7, or 14 days, when lung structure was assessed by stereology. A 40% or 60% O2 exposure reduced alveoli number from 4.20×106 (at 21% O2) to 3.55×106 (P=0.0002) or 2.99×106 (P=0.0323), respectively, without impact on septal thickness. At 85% O2, alveoli number was reduced to 1.37×106 (P<0.0001), and septal thickness was increased (from 10.00 µm to 11.96 µm, P=0.0294). An 85%-O2 exposure for the first 4 h of life followed by room air exposure reduced alveoli number from 4.20×106 to 3.35×106 (P=0.0042) and increased septal thickness (from 10.00 µm to 11.81 µm, P=0.0082). A 24-h 85% O2 exposure on day 1 reduced alveoli number at day 14 to 3.51×106 (P=0.0155), while a 7-day 85% O2 exposure dramatically decreased alveoli number to 2.11×106 (P<0.0001) by day 14; where septal thickness was increased to 12.87 µm (P<0.0001). These data - the first stereological analysis of lung alveolarisation in the BPD hyperoxia model - indicate that the alveolarisation arrest is dependent upon the O2 concentration and duration, and that the effect of the shift from 85% O2 to 21% O2 on septal thickness is dependent on this timing of the transition. These data suggest that continuous exposure of the developing mouse lung to 85% O2 for 14 days, best recapitulates both changes in alveolar number and septal thickness.

  • Lung growth/development
  • Neonates
  • Cell biology
  • Copyright ©the authors 2016
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Refinement of the hyperoxia-based experimental mouse model of bronchopulmonary dysplasia
Claudio Nardiello, Ivana Mizíková, Jordi Ruiz-Camp, Werner Seeger, Rory Morty
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4027; DOI: 10.1183/13993003.congress-2016.PA4027

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Refinement of the hyperoxia-based experimental mouse model of bronchopulmonary dysplasia
Claudio Nardiello, Ivana Mizíková, Jordi Ruiz-Camp, Werner Seeger, Rory Morty
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4027; DOI: 10.1183/13993003.congress-2016.PA4027
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