Animal models of bronchopulmonary dysplasia. The preterm and term rabbit models

Abstract

Bronchopulmonary dysplasia (BPD) is an important lung developmental pathophysiology that affects many premature infants each year. Newborn animal models employing both premature and term animals have been used over the years to study various components of BPD. This review describes some of the neonatal rabbit studies that have contributed to the understanding of BPD, including those using term newborn hyperoxia exposure models, premature hyperoxia models, and a term newborn hyperoxia model with recovery in moderate hyperoxia, all designed to emulate aspects of BPD in human infants. Some investigators perturbed these models to include exposure to neonatal infection/inflammation or postnatal malnutrition. The similarities to lung injury in human premature infants include an acute inflammatory response with the production of cytokines, chemokines, and growth factors that have been implicated in human disease, abnormal pulmonary function, disordered lung architecture, and alveolar simplification, development of fibrosis, and abnormal vascular growth factor expression. Neonatal rabbit models have the drawback of limited access to reagents as well as the lack of readily available transgenic models but, unlike smaller rodent models, are able to be manipulated easily and are significantly less expensive than larger animal models.

Caffeine Prevents Hyperoxia-Induced Functional and Structural Lung Damage in Preterm Rabbits

“…Similarities between rabbit and human lung development make these results useful to understand initial changes and potential benefits of caffeine therapy in preterm infants, supporting its use in current and future trials of BPD prevention and treatment [12]. …”

“…It is also possible to test lung function in pups. Furthermore, rabbits have a relatively short gestation with a large litter size [12]. Larger animals like sheep and nonhuman primates have also contributed to understanding and treating BPD, but their housing demands and costs are substantial [13,14].…”

Can We Understand the Pathobiology of Bronchopulmonary Dysplasia?

“…Currently, there is little standardization across studies, regarding both the animals, and the injurious stimuli employed. BPD may be modeled in mice 172 , rats 173 , rabbits 174 , lambs 175 , pigs 176, 177 , and non-human primates 178 , and these models have proved highly valuable in studies on pathobiology 179 and therapy development 180 . Recent reports have documented no less than 40 different hyperoxia exposure protocols used in a two-year period – in mice alone – to study BPD 181, 182 .…”

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).…”