Looking ahead: where to next for animal models of bronchopulmonary dysplasia?

Abstract

Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, with appreciable morbidity and mortality in a neonatal intensive care setting. Much interest has been shown in the identification of pathogenic pathways that are amenable to pharmacological manipulation (1) to facilitate the development of novel therapeutic and medical management strategies and (2) to identify the basic mechanisms of late lung development, which remains poorly understood. A number of animal models have therefore been developed and continue to be refined with the aim of recapitulating pathological pulmonary hallmarks noted in lungs from neonates with BPD. These animal models rely on several injurious stimuli, such as mechanical ventilation or oxygen toxicity and infection and sterile inflammation, as applied in mice, rats, rabbits, pigs, lambs and nonhuman primates. This review addresses recent developments in modeling BPD in experimental animals and highlights important neglected areas that demand attention. Additionally, recent progress in the quantitative microscopic analysis of pathology tissue is described, together with new in vitro approaches of value for the study of normal and aberrant alveolarization. The need to examine long-term sequelae of damage to the developing neonatal lung is also considered, as is the need to move beyond the study of the lungs alone in experimental animal models of BPD.

Stereological analysis of individual lung lobes during normal and aberrant mouse lung alveolarisation

“…These data validated the utility of hyperoxia in the present study as a viable injurious stimulus to limit proper lung alveolarisation in this experimental animal model of BPD (Nardiello et al. ,b).…”

Can We Understand the Pathobiology of Bronchopulmonary Dysplasia?

“…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 . The recognition that the lung response to injuries such as hyperoxia is highly dependent on mouse strain, has stimulated efforts to standardize experimental models of hyperoxia, by directly comparing either strain or specific injury protocols, in an effort to make studies performed in different laboratories directly comparable.…”

Recombinant CCN1 prevents hyperoxia-induced lung injury in neonatal rats

“…Although the current study focuses on oxygen-induced lung injury which has phenotypic features similar to BPD, future studies are needed to investigate the role of CCN1 in the pathogenesis of BPD induced by other risk factors. In addition, more advanced stereological and three dimensional approaches to assess lung alveolar structure have been recently reported (38) and these techniques will provide new insights into architectural changes in experimental models of BPD.…”