Animal models of bronchopulmonary dysplasia. The term mouse models

Abstract

Berger J, Bhandari V. Animal models of bronchopulmonary dysplasia. I. The term mouse models. Am J Physiol Lung Cell Mol Physiol 307: L936 -L947, 2014. First published October 10, 2014 doi:10.1152/ajplung.00159.2014.-The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante-and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.

Collagen and elastin cross-linking is altered during aberrant late lung development associated with hyperoxia

“…There is also evidence of altered elastin turnover, as assessed by urinary excretion of the desmosine elastin cross-link, in infants with BPD (12). These data point to disturbances to ECM production and processing in BPD, which may be mimicked in animal models, employing either hyperoxia, caloric restriction, mechanical ventilation, or preterm delivery as an injurious stimulus in rats, mice, lambs, and baboons (6,13,49,66). The lung histopathology that results is reminiscent of that of BPD in humans, with evident air space enlargement, septal wall thickening, and a reduced number of alveoli, as well as perturbations to ECM structures.…”

Protein Kinase Cζ Inhibitor Promotes Resolution of Bleomycin-Induced Acute Lung Injury

“…Animal models to study the effects of noxious stimuli on lung development in BPD have focused on prenatal endotoxin exposure, postnatal hyperoxia or hypoxia, and mechanical ventilation (20,21,44). To the best of our knowledge, this is one of the first studies to examine the mechanisms underlying systemic sepsis-induced lung remodeling, which is observed in premature infants who develop " new BPD" without significant exposure to hyperoxia or ventilation (2).…”

“…Traditionally, rodent models of BPD have used hyperoxia, antenatal endotoxin exposure, and mechanical ventilation to induce acute lung inflammation and alveolar remodeling in the immature lung (20,21). Although it is accepted that systemic sepsis in the premature infant is a major risk factor for the development of BPD, the mechanisms by which sepsis-induced acute lung inflammation contributes to alveolar simplification in BPD remain poorly understood (11,22,23).…”

Coming to terms with tissue engineering and regenerative medicine in the lung

“…In turn, these ECM components are themselves modulated by diseases such as asthma, COPD, and pulmonary fibrosis (i.e., many of the same diseases that are indications for lung transplantation). Factors such as altered oxygen levels (2,16,69,110,120,157,210,221,226), environmental influences (23,211), and inflammatory and profibrotic mediators (3,4,9,30,154,209,229) can modulate the expression of collagens, fibronectin, elastin. and other important lung ECM components.…”