An Experimental Model of Bronchopulmonary Dysplasia Features Long-Term Retinal and Pulmonary Defects but Not Sustained Lung Inflammation
Bronchopulmonary dysplasia (BPD) is a severe lung disease that affects preterm infants receiving oxygen therapy. No standardized, clinically-relevant BPD model exists, hampering efforts to understand and treat this disease. This study aimed to evaluate and confirm a candidate model of acute and chro...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2021.689699/full |
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| author | Lakshanie C. Wickramasinghe Peter van Wijngaarden Peter van Wijngaarden Chad Johnson Evelyn Tsantikos Margaret L. Hibbs |
| author_facet | Lakshanie C. Wickramasinghe Peter van Wijngaarden Peter van Wijngaarden Chad Johnson Evelyn Tsantikos Margaret L. Hibbs |
| author_sort | Lakshanie C. Wickramasinghe |
| collection | DOAJ |
| description | Bronchopulmonary dysplasia (BPD) is a severe lung disease that affects preterm infants receiving oxygen therapy. No standardized, clinically-relevant BPD model exists, hampering efforts to understand and treat this disease. This study aimed to evaluate and confirm a candidate model of acute and chronic BPD, based on exposure of neonatal mice to a high oxygen environment during key lung developmental stages affected in preterm infants with BPD. Neonatal C57BL/6 mouse pups were exposed to 75% oxygen from postnatal day (PN)-1 for 5, 8, or 14 days, and their lungs were examined at PN14 and PN40. While all mice showed some degree of lung damage, mice exposed to hyperoxia for 8 or 14 days exhibited the greatest septal wall thickening and airspace enlargement. Furthermore, when assessed at PN40, mice exposed for 8 or 14 days to supplemental oxygen exhibited augmented septal wall thickness and emphysema, with the severity increased with the longer exposure, which translated into a decline in respiratory function at PN80 in the 14-day model. In addition to this, mice exposed to hyperoxia for 8 days showed significant expansion of alveolar epithelial type II cells as well as the greatest fibrosis when assessed at PN40 suggesting a healing response, which was not seen in mice exposed to high oxygen for a longer period. While evidence of lung inflammation was apparent at PN14, chronic inflammation was absent from all three models. Finally, exposure to high oxygen for 14 days also induced concurrent outer retinal degeneration. This study shows that early postnatal exposure to high oxygen generates hallmark acute and chronic pathologies in mice that highlights its use as a translational model of BPD. |
| first_indexed | 2024-12-17T10:22:43Z |
| format | Article |
| id | doaj.art-9205e01022844f6fad8e283f77a97d7d |
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| language | English |
| last_indexed | 2024-12-17T10:22:43Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-9205e01022844f6fad8e283f77a97d7d2022-12-21T21:52:44ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602021-08-01910.3389/fped.2021.689699689699An Experimental Model of Bronchopulmonary Dysplasia Features Long-Term Retinal and Pulmonary Defects but Not Sustained Lung InflammationLakshanie C. Wickramasinghe0Peter van Wijngaarden1Peter van Wijngaarden2Chad Johnson3Evelyn Tsantikos4Margaret L. Hibbs5Leukocyte Signalling Laboratory, Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, AustraliaDepartment of Surgery - Ophthalmology, University of Melbourne, Melbourne, VIC, AustraliaCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, AustraliaMonash Micro Imaging, Alfred Research Alliance, Monash University, Melbourne, VIC, AustraliaLeukocyte Signalling Laboratory, Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, AustraliaLeukocyte Signalling Laboratory, Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, VIC, AustraliaBronchopulmonary dysplasia (BPD) is a severe lung disease that affects preterm infants receiving oxygen therapy. No standardized, clinically-relevant BPD model exists, hampering efforts to understand and treat this disease. This study aimed to evaluate and confirm a candidate model of acute and chronic BPD, based on exposure of neonatal mice to a high oxygen environment during key lung developmental stages affected in preterm infants with BPD. Neonatal C57BL/6 mouse pups were exposed to 75% oxygen from postnatal day (PN)-1 for 5, 8, or 14 days, and their lungs were examined at PN14 and PN40. While all mice showed some degree of lung damage, mice exposed to hyperoxia for 8 or 14 days exhibited the greatest septal wall thickening and airspace enlargement. Furthermore, when assessed at PN40, mice exposed for 8 or 14 days to supplemental oxygen exhibited augmented septal wall thickness and emphysema, with the severity increased with the longer exposure, which translated into a decline in respiratory function at PN80 in the 14-day model. In addition to this, mice exposed to hyperoxia for 8 days showed significant expansion of alveolar epithelial type II cells as well as the greatest fibrosis when assessed at PN40 suggesting a healing response, which was not seen in mice exposed to high oxygen for a longer period. While evidence of lung inflammation was apparent at PN14, chronic inflammation was absent from all three models. Finally, exposure to high oxygen for 14 days also induced concurrent outer retinal degeneration. This study shows that early postnatal exposure to high oxygen generates hallmark acute and chronic pathologies in mice that highlights its use as a translational model of BPD.https://www.frontiersin.org/articles/10.3389/fped.2021.689699/fullbronchopulmonary dysplasialung developmentinflammationanimal modelsupplemental oxygenchronic obstructive pulmonary disease |
| spellingShingle | Lakshanie C. Wickramasinghe Peter van Wijngaarden Peter van Wijngaarden Chad Johnson Evelyn Tsantikos Margaret L. Hibbs An Experimental Model of Bronchopulmonary Dysplasia Features Long-Term Retinal and Pulmonary Defects but Not Sustained Lung Inflammation Frontiers in Pediatrics bronchopulmonary dysplasia lung development inflammation animal model supplemental oxygen chronic obstructive pulmonary disease |
| title | An Experimental Model of Bronchopulmonary Dysplasia Features Long-Term Retinal and Pulmonary Defects but Not Sustained Lung Inflammation |
| title_full | An Experimental Model of Bronchopulmonary Dysplasia Features Long-Term Retinal and Pulmonary Defects but Not Sustained Lung Inflammation |
| title_fullStr | An Experimental Model of Bronchopulmonary Dysplasia Features Long-Term Retinal and Pulmonary Defects but Not Sustained Lung Inflammation |
| title_full_unstemmed | An Experimental Model of Bronchopulmonary Dysplasia Features Long-Term Retinal and Pulmonary Defects but Not Sustained Lung Inflammation |
| title_short | An Experimental Model of Bronchopulmonary Dysplasia Features Long-Term Retinal and Pulmonary Defects but Not Sustained Lung Inflammation |
| title_sort | experimental model of bronchopulmonary dysplasia features long term retinal and pulmonary defects but not sustained lung inflammation |
| topic | bronchopulmonary dysplasia lung development inflammation animal model supplemental oxygen chronic obstructive pulmonary disease |
| url | https://www.frontiersin.org/articles/10.3389/fped.2021.689699/full |
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