Functional and pathological effects of prolonged hyperoxia in neonatal mice.
Bronchopulmonary dysplasia (BPD) commonly develops in premature infants. An improved understanding of the pathophysiology of BPD requires better models. In this study, neonatal FVB/N mice were exposed to room air or 85% oxygen for 28 days. Neonatal hyperoxia resulted in decreased alveolar septation, increased terminal air space size, and increased lung fibrosis. These changes were evident after 7 days and more pronounced by 28 days. Decreased alveolarization was preceded by decreased proliferation of lung cells. After 3 days of hyperoxia, cell proliferation was decreased compared with room air littermates. Cell proliferation continued to be decreased in the first 2 wk but normalized by 4 wk. Hyperoxia caused an increased number of inflammatory cells in lung tissue and in lung lavage fluid. Analysis of lung tissue RNA by RT-PCR showed that hyperoxia increased expression of the proinflammatory cytokines interleukin-1alpha and macrophage inflammatory protein-1alpha. Prolonged neonatal hyperoxia caused functional changes, decreasing lung volume and pulmonary compliance. We conclude that prolonged exposure of neonatal mice to hyperoxia creates a lesion that is very similar to human BPD and suggests that altered cell proliferation may be important in the pathogenesis of chronic neonatal lung disease.
Division of Neonatology and Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
B B
BB
Warner
L A
LA
Stuart
R A
RA
Papes
J R
JR
Wispé
D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia; D002455:Cell Division; D054407:Chemokine CCL4; D005786:Gene Expression Regulation; D006801:Humans; D018496:Hyperoxia / Q000473:pathology / Q000503:physiopathology*; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology* / Q000503:physiopathology*; D008170:Lung Compliance; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D010100:Oxygen / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000473:pathology / Q000503:physiopathology; D012016:Reference Values
D054407:Chemokine CCL4; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D010100:Oxygen