A rat model establishment of bronchopulmonary dysplasia-related lung & brain injury within 28 days after birth.

PURPOSE: Lung injury associated with bronchopulmonary dysplasia (BPD) and its related neurodevelopmental disorders have garnered increasing attention in the context of premature infants. Establishing a reliable animal model is essential for delving into the underlying mechanisms of these conditions.

METHODS

Newborn rats were randomly assigned to two groups: the hyperoxia-induced BPD group and the normoxia (NO) group. For the BPD group, they were nurtured in a hyperoxic environment with a high oxygen inspired fraction (0.85) from birth until day 14 within 28 days postnatally. In contrast, the NO group consisted of newborn rats that were nurtured in a normoxic environment with a standard oxygen inspired fraction (0.21) for 28 days postnatally. Various pathological sections of both lung and brain tissues were examined. TUNEL staining, immunofluorescence assays, and functional tests were performed, and the results were meticulously analyzed to assess the impact of hyperoxia environments on the developing organs.

RESULTS

In the newborn rats of the BPD group, a significant reduction in alveolar number coupled with enlargement was observed, alongside severe fibrosis, collagen deposition, and constriction of bronchi and vascular lumens. This was accompanied by an accumulation of inflammatory cells and a marked deterioration in lung function compared to the NO group (P < 0.05). Additionally, a decrease in neuronal count, an increase in neuronal apoptosis, proliferation of neuroglia cells, and demyelination were noted, and poorer performance in the Morris water maze test within the BPD group (P < 0.05).

CONCLUSION

The BPD-rats model was established successfully. Lung injury in the BPD group evident across the bronchi to the alveoli and pulmonary vessels, which was associated with deteriorated lung function at postnatal day 14. Concurrently, brain injury extended from the cerebral cortex to the hippocampus, which was associated with impaired performance in orientation navigation and spatial probe tests at postnatal day 28.