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Our objective was to develop a robust hyperoxia\u2011based mouse model of BPD that recapitulated the pathological perturbations to lung structure noted in infants with BPD. Newborn mouse pups were exposed to a varying fraction of oxygen in the inspired air (FiO2) and a varying window of hyperoxia exposure, after which lung structure was assessed by design\u2011based stereology with systemic uniform random sampling. The efficacy of a candidate therapeutic intervention using parenteral nutrition was evaluated to demonstrate the utility of the standardised BPD model for drug discovery. An FiO2 0.85 for the first 14 days of life decreased total alveoli number and concomitantly increased alveolar septal wall thickness, which are two key histopathological characteristics of BPD. A reduction in FiO2 to 0.60 or 0.40 also caused a decrease in the total alveoli number, but the septal wall thickness was not impacted. Neither a decreasing oxygen gradient (from FiO2 0.85 to 0.21 over the first 14 days of life) nor an oscillation in FiO2 (between 0.85 and 0.40 on a 24 h:24 h cycle) had an appreciable impact on lung development. The risk of missing beneficial effects of therapeutic interventions at FiO2 0.85, using parenteral nutrition as an intervention in the model was also noted; highlighting the utility of lower FiO2 in selected studies, and underscoring the need to tailor the model employed to the experimental intervention. Thus, a state-of-the-art BPD animal model that recapitulated the two histopathological hallmark perturbations to lung architecture associated with BPD is described. The model presented here, where injurious stimuli have been systematically evaluated, provides the most promising approach for the development of new strategies to drive post-natal lung maturation in affected infants.<\/jats:p>","DOI":"10.1242\/dmm.027086","type":"journal-article","created":{"date-parts":[[2017,1,9]],"date-time":"2017-01-09T16:05:08Z","timestamp":1483977908000},"source":"Crossref","is-referenced-by-count":75,"title":["Modelling bronchopulmonary dysplasia in mice: how much oxygen is enough?"],"prefix":"10.1242","author":[{"given":"Claudio","family":"Nardiello","sequence":"first","affiliation":[{"name":"Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany"},{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Mi\u017e\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany"},{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany"},{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Ruiz-Camp","sequence":"additional","affiliation":[{"name":"Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany"},{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Vad\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Herold","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[{"name":"Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany"},{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory E.","family":"Morty","sequence":"additional","affiliation":[{"name":"Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany"},{"name":"Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL), Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2016,1,1]]},"reference":[{"key":"2021042500005079500_DMM027086C1","doi-asserted-by":"publisher","first-page":"L537","DOI":"10.1152\/ajplung.00050.2006","article-title":"Hyperoxia modulates TGF-beta\/BMP signaling in a mouse model of bronchopulmonary dysplasia","volume":"292","author":"Alejandre-Alc\u00e1zar","year":"2007","journal-title":"Am. 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