Single, double, and triple-hit strategies to establish a long-term premature rabbit model of bronchopulmonary dysplasia
Abstract Background Bronchopulmonary dysplasia (BPD) is a chronic lung condition of premature neonates, yet without an established pharmacological treatment. The BPD rabbit model exposed to 95% oxygen has been used in recent years for drug testing. However, the toxicity of the strong hyperoxic hit p...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12931-024-03053-0 |
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| author | Chiara Catozzi Francesca Stretti Enrica Scalera Matteo Storti Angelo Modena Giorgio Aquila Gino Villetti Erica Ferrini Andrea Grandi Franco Fabio Stellari Francesca Ravanetti Luisa Ragionieri Roberta Ciccimarra Matteo Zoboli Christina Brandenberger Henri Schulte Xabier Murgia Maurizio Civelli Francesca Ricci |
| author_facet | Chiara Catozzi Francesca Stretti Enrica Scalera Matteo Storti Angelo Modena Giorgio Aquila Gino Villetti Erica Ferrini Andrea Grandi Franco Fabio Stellari Francesca Ravanetti Luisa Ragionieri Roberta Ciccimarra Matteo Zoboli Christina Brandenberger Henri Schulte Xabier Murgia Maurizio Civelli Francesca Ricci |
| author_sort | Chiara Catozzi |
| collection | DOAJ |
| description | Abstract Background Bronchopulmonary dysplasia (BPD) is a chronic lung condition of premature neonates, yet without an established pharmacological treatment. The BPD rabbit model exposed to 95% oxygen has been used in recent years for drug testing. However, the toxicity of the strong hyperoxic hit precludes a longer-term follow-up due to high mortality after the first week of life. This study aimed to extend the preterm rabbit model to postnatal day (PND) 14 to mimic the evolving phase of BPD and enable the investigation of therapeutic interventions at later and more relevant time points. Methods Preterm rabbit pups delivered on the 28th day of gestation were either exposed to room air or different degrees of hyperoxia (50% and 70% O2) for 14 days. Single (immediately after birth) or double (at birth and at PND5) intratracheal lipopolysaccharide (LPS) administrations were also tested in combination with 50% O2. Age-matched rabbits delivered vaginally at term were used as controls. Survival, weight gain, lung function, pulmonary artery micro-ultrasound Doppler analysis, lung histology (alveolarization, lung injury score, and design-based stereology), and longitudinal micro-CT imaging were used to compare the outcomes at PND14. Results Premature birth itself, without any other BPD hit, was associated with lung function deficits, delayed lung development, and cardiovascular abnormalities. The BPD-like lung phenotype was enhanced by 70% O2 but not by 50% O2 hyperoxia. Intratracheal LPS delivered immediately after birth was associated with significantly higher lung injury scores at PND14 and increased tissue damping, a marker of parenchymal air resistance. Conclusion Several strategies are feasible to extend the preterm rabbit model of BPD to PND14. Preterm birth at the saccular phase itself, even in the absence of other postnatal BPD hits, was associated with lung function deficits, delayed lung development, and cardiovascular abnormalities compared with age-matched term rabbit pups. Enhanced BPD-like phenotypes can be further achieved by continued exposure to moderate hyperoxia (70% O2) and the intratracheal administration of LPS. |
| format | Article |
| id | doaj-art-8232b47f15c3420dbd94bbcc5f23a935 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Respiratory Research |
| spelling | doaj-art-8232b47f15c3420dbd94bbcc5f23a9352025-01-26T12:48:56ZengBMCRespiratory Research1465-993X2025-01-0126111410.1186/s12931-024-03053-0Single, double, and triple-hit strategies to establish a long-term premature rabbit model of bronchopulmonary dysplasiaChiara Catozzi0Francesca Stretti1Enrica Scalera2Matteo Storti3Angelo Modena4Giorgio Aquila5Gino Villetti6Erica Ferrini7Andrea Grandi8Franco Fabio Stellari9Francesca Ravanetti10Luisa Ragionieri11Roberta Ciccimarra12Matteo Zoboli13Christina Brandenberger14Henri Schulte15Xabier Murgia16Maurizio Civelli17Francesca Ricci18Chiesi Farmaceutici, R&D DepartmentDepartment of Veterinary Sciences, University of ParmaChiesi Farmaceutici, R&D DepartmentChiesi Farmaceutici, R&D DepartmentDepartment of Veterinary Sciences, University of ParmaChiesi Farmaceutici, R&D DepartmentChiesi Farmaceutici, R&D DepartmentChiesi Farmaceutici, R&D DepartmentChiesi Farmaceutici, R&D DepartmentChiesi Farmaceutici, R&D DepartmentDepartment of Veterinary Sciences, University of ParmaDepartment of Veterinary Sciences, University of ParmaDepartment of Veterinary Sciences, University of ParmaDepartment of Veterinary Sciences, University of ParmaInstitut für Funktionelle Anatomie Charité – UniversitätsmedizinInstitute of Functional and Applied Anatomy, Hannover Medical SchoolScientific ConsultantChiesi Farmaceutici, R&D DepartmentChiesi Farmaceutici, R&D DepartmentAbstract Background Bronchopulmonary dysplasia (BPD) is a chronic lung condition of premature neonates, yet without an established pharmacological treatment. The BPD rabbit model exposed to 95% oxygen has been used in recent years for drug testing. However, the toxicity of the strong hyperoxic hit precludes a longer-term follow-up due to high mortality after the first week of life. This study aimed to extend the preterm rabbit model to postnatal day (PND) 14 to mimic the evolving phase of BPD and enable the investigation of therapeutic interventions at later and more relevant time points. Methods Preterm rabbit pups delivered on the 28th day of gestation were either exposed to room air or different degrees of hyperoxia (50% and 70% O2) for 14 days. Single (immediately after birth) or double (at birth and at PND5) intratracheal lipopolysaccharide (LPS) administrations were also tested in combination with 50% O2. Age-matched rabbits delivered vaginally at term were used as controls. Survival, weight gain, lung function, pulmonary artery micro-ultrasound Doppler analysis, lung histology (alveolarization, lung injury score, and design-based stereology), and longitudinal micro-CT imaging were used to compare the outcomes at PND14. Results Premature birth itself, without any other BPD hit, was associated with lung function deficits, delayed lung development, and cardiovascular abnormalities. The BPD-like lung phenotype was enhanced by 70% O2 but not by 50% O2 hyperoxia. Intratracheal LPS delivered immediately after birth was associated with significantly higher lung injury scores at PND14 and increased tissue damping, a marker of parenchymal air resistance. Conclusion Several strategies are feasible to extend the preterm rabbit model of BPD to PND14. Preterm birth at the saccular phase itself, even in the absence of other postnatal BPD hits, was associated with lung function deficits, delayed lung development, and cardiovascular abnormalities compared with age-matched term rabbit pups. Enhanced BPD-like phenotypes can be further achieved by continued exposure to moderate hyperoxia (70% O2) and the intratracheal administration of LPS.https://doi.org/10.1186/s12931-024-03053-0Premature birthBronchopulmonary dysplasiaBPDPreterm rabbitsmicro-CTHyperoxia |
| spellingShingle | Chiara Catozzi Francesca Stretti Enrica Scalera Matteo Storti Angelo Modena Giorgio Aquila Gino Villetti Erica Ferrini Andrea Grandi Franco Fabio Stellari Francesca Ravanetti Luisa Ragionieri Roberta Ciccimarra Matteo Zoboli Christina Brandenberger Henri Schulte Xabier Murgia Maurizio Civelli Francesca Ricci Single, double, and triple-hit strategies to establish a long-term premature rabbit model of bronchopulmonary dysplasia Respiratory Research Premature birth Bronchopulmonary dysplasia BPD Preterm rabbits micro-CT Hyperoxia |
| title | Single, double, and triple-hit strategies to establish a long-term premature rabbit model of bronchopulmonary dysplasia |
| title_full | Single, double, and triple-hit strategies to establish a long-term premature rabbit model of bronchopulmonary dysplasia |
| title_fullStr | Single, double, and triple-hit strategies to establish a long-term premature rabbit model of bronchopulmonary dysplasia |
| title_full_unstemmed | Single, double, and triple-hit strategies to establish a long-term premature rabbit model of bronchopulmonary dysplasia |
| title_short | Single, double, and triple-hit strategies to establish a long-term premature rabbit model of bronchopulmonary dysplasia |
| title_sort | single double and triple hit strategies to establish a long term premature rabbit model of bronchopulmonary dysplasia |
| topic | Premature birth Bronchopulmonary dysplasia BPD Preterm rabbits micro-CT Hyperoxia |
| url | https://doi.org/10.1186/s12931-024-03053-0 |
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