Functional and pathological effects of prolonged hyperoxia in neonatal mice

Abstract

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-1α and macrophage inflammatory protein-1α. 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.

The Role of Angiopoietin 2 in Hyperoxia-Inuduced Acute Lung Injury

“…1 Acute pulmonary injury secondary to hyperoxia is complex and multifactorial. 2 Hyperoxia-induced acute lung injury (HALI) is characterized by an extensive inflammatory response and destruction of the alveolarcapillary barrier. [3][4][5][6] The inflammatory cell influx is orchestrated and amplified by chemotactic factors.…”

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

“…Although the use of milder ventilation strategies, exogenous surfactant, and antenatal steroids has reduced the incidence of airway inflammation and fibrosis, infants dying from BPD have simplified alveoli that are less vascularized (2). Likewise, alveolar simplification and disorganized vasculature is seen in preterm baboons (3,4) and in term rodents exposed to hyperoxia at birth (5,6). Oxidative stress caused by high oxygen exposure or by the inflammatory response to oxygen-induced cell injury promotes alveolar simplification by suppressing expression of angiogenic factors such as vascular endothelial cell growth factor (VEGF) (for review, see Ref.…”

Neonatal Hyperoxia Causes Pulmonary Vascular Disease and Shortens Life Span in Aging Mice

“…6 Analogous to the pathology seen in these infants, exposure of newborn rodents to Ն85% oxygen for 10 to 14 days causes alveolar simplification and abnormal vascular development. 7,8 The oxygen-dependent loss of vascular endothelial cell growth factor (VEGF) likely contributes to these changes. 9 -11 Blocking VEGF signaling disrupts postnatal alveolar development, [12][13][14] and VEGF gene therapy can partially protect the developing rat lung against hyperoxia.…”