Animal models of bronchopulmonary dysplasia. The preterm baboon models

Abstract

Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, has been aided by investigations of multiple animal models, including the neonatal baboon (Papio species). In this article we highlight how the preterm baboon model at both 140 and 125 days gestation (term equivalent 185 days) has advanced our understanding and management of the immature human infant with neonatal lung disease. Not only is the 125-day baboon model extremely relevant to the condition of bronchopulmonary dysplasia but there are also critical neurodevelopmental and other end-organ pathological features associated with this model not fully discussed in this limited forum. We also describe efforts to incorporate perinatal infection into these preterm models, both fetal and neonatal, and particularly associated with Ureaplasma/Mycoplasma organisms. Efforts to rekindle the preterm primate model for future evaluations of therapies such as stem cell replacement, early lung recruitment interventions coupled with noninvasive surfactant and high-frequency nasal ventilation, and surfactant therapy coupled with antioxidant or anti-inflammatory medications, to name a few, should be undertaken.

Keywords: baboon; bronchopulmonary dysplasia; lung; preterm infant; ureaplasma.

Fig. 1.

The 125-day model; early [extubation nasal continuous positive airway pressure (nCPAP) at 24 h] vs. delayed nCPAP (extubation to nCPAP at 5 days). A: in this lung from an early nCPAP animal treated for 28 days, the terminal bronchiolar wall (b) shows no evidence of mural inflammation and its branches into respiratory bronchioles and subjacent saccules/alveoli show well-expanded, thinned walls. B: conversely, the 28-day delayed nCPAP-treated lung had thickened and more cellular bronchiolar and saccular/alveolar walls. Hematoxylin and eosin; original magnification ×10. Reprinted from Ref. with permission.

Fig. 2.

The 125-day model; antenatal intra-amniotic Ureaplasma urealyticum treatment, 14-day model. A: baseline appearance of an uninfected animal ventilated for 14 days: very few inflammatory cells in the bronchiolar wall but more obvious interstitial cellularity in the alveolar walls. B: lung of an animal with low/no tracheal U. urealyticum colony-forming units shows focal bronchiolitis and patchy increased inflammatory cells in the subjacent alveolar walls. C: lung from the most severely infected animal shows a dense inflammatory cell infiltrate in the bronchiolar wall as well as the intra-alveolar and interstitial compartments. Hematoxylin and eosin; original magnification ×10. Reprinted from Ref. with permission.