title: Bronchopulmonary dysplasia in a double-hit mouse model induced by intrauterine hypoxia and postnatal hyperoxia: closer to clinical features?
abstract: Despite increased survival of very preterm newborns, bronchopulmonary dysplasia (BPD) remains a major threat, as it affects long-term pulmonary function and neurodevelopmental outcome. Recent research focused on mechanisms of lung repair. Animal models of BPD in term rodents use postnatal hyperoxia in order to mimic features observed in very preterm human neonates: reduced alveolarization and impaired septal architecture without profound inflammatory changes. In contrast, BPD in very preterm human neonates involves prenatal hits e.g. infections and growth restriction plus postnatal ventilation. BPD induced in rodents by postnatal hyperoxia also exhibits reduced alveolarization however without septal pathology but with marked inflammation. We therefore aimed to establish an animal model combining prenatal growth restriction (FiO₂ 0.1 for 4 days) with postnatal hyperoxia (FiO₂ 0.7 for 2 weeks). In double-hit mice the development was retarded: body weight and length, lung and brain weight were significantly reduced by day P14 compared with normoxic controls. Histomorphometric analysis revealed reduced alveolarization and increased septal thickness without pronounced inflammatory lesions. A down-regulation of SftpB and SftpC genes was observed in double-hit animals compared with controls. Thus, we established a new model of BPD using pre- and postnatal hits.
authors.affiliation: Department of Pediatrics and Neonatology, Saarland University, Homburg, Saar, Germany. Electronic address: ludwig.gortner@uks.eu.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Gortner
authors.affiliation: Department of Pediatrics and Neonatology, Saarland University, Homburg, Saar, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Monz
authors.affiliation: Department of Pediatrics and Neonatology, Saarland University, Homburg, Saar, Germany.
authors.forename: Céline
authors.initials: C
authors.lastname: Mildau
authors.affiliation: Department of Pediatrics and Neonatology, Saarland University, Homburg, Saar, Germany; Department of Pediatrics, Daping Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Pediatrics and Neonatology, Saarland University, Homburg, Saar, Germany.
authors.forename: Mariz
authors.initials: M
authors.lastname: Kasoha
authors.affiliation: Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Saar, Germany.
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Laschke
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Torge
authors.initials: T
authors.lastname: Roolfs
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmiedl
authors.affiliation: Institute of Anatomy and Cell Biology, Saarland University, Homburg, Saar, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Meier
authors.affiliation: Department of Pediatrics and Neonatology, Saarland University, Homburg, Saar, Germany.
authors.forename: Erol
authors.initials: E
authors.lastname: Tutdibi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology; D001997:Bronchopulmonary Dysplasia / Q000150:complications / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005311:Fetal Hypoxia / Q000209:etiology / Q000473:pathology*; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006128:Growth / Q000502:physiology; D018496:Hyperoxia / Q000209:etiology / Q000473:pathology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D011247:Pregnancy; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016207:Cytokines; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger