A Novel Model for Simultaneous Evaluation of Hyperoxia-Mediated Brain and Lung Injury in Neonatal Rats
Despite improved neonatal intensive care, the risk of premature-born infants developing bronchopulmonary dysplasia (BPD) and encephalopathy of prematurity (EoP) remains high. With hyperoxia being a major underlying factor, both preterm-birth-related complications are suggested to be closely interrel...
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2025-03-01
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| author | Stefanie Obst Meray Serdar Josephine Herz Karina Kempe Meriem Assili Mandana Rizazad Dharmesh Hirani Miguel A. Alejandre Alcazar Stefanie Endesfelder Marius A. Möbius Mario Rüdiger Ursula Felderhoff-Müser Ivo Bendix |
| author_facet | Stefanie Obst Meray Serdar Josephine Herz Karina Kempe Meriem Assili Mandana Rizazad Dharmesh Hirani Miguel A. Alejandre Alcazar Stefanie Endesfelder Marius A. Möbius Mario Rüdiger Ursula Felderhoff-Müser Ivo Bendix |
| author_sort | Stefanie Obst |
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| description | Despite improved neonatal intensive care, the risk of premature-born infants developing bronchopulmonary dysplasia (BPD) and encephalopathy of prematurity (EoP) remains high. With hyperoxia being a major underlying factor, both preterm-birth-related complications are suggested to be closely interrelated. However, experimental models are lacking for the assessment of the potentially close interplay between both organs. To establish a model, suitable for the assessment of both affected organs, Wistar rats were exposed to 80% oxygen from postnatal day 2 (P2) for seven days. Brain and lung tissues were analysed via histomorphometry, immunohistochemistry, real-time PCR, and western blot at term P11. In the brain, hyperoxia induced significant hypomyelination accompanied by a reduction in oligodendrocytes and CD68 expression on microglia cells. These changes correlate with arrested alveolarisation and an increased number of macrophages in the lung. Interestingly, in contrast to the reduced formation of pulmonary microvessels, an increased vascular density was detected in the brain. Seven days of hyperoxia induces typical characteristics of BPD and EoP in neonatal rats, thereby linking impaired alveolarisation with disturbed myelination in the brain and providing an experimental model for understanding pathophysiological mechanisms and identifying organ-spanning novel therapeutic interventions targeting both diseases. |
| format | Article |
| id | doaj-art-db296fa2b7fc417cbf8251f610fa3404 |
| institution | OA Journals |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-db296fa2b7fc417cbf8251f610fa34042025-08-20T02:11:22ZengMDPI AGCells2073-44092025-03-0114644310.3390/cells14060443A Novel Model for Simultaneous Evaluation of Hyperoxia-Mediated Brain and Lung Injury in Neonatal RatsStefanie Obst0Meray Serdar1Josephine Herz2Karina Kempe3Meriem Assili4Mandana Rizazad5Dharmesh Hirani6Miguel A. Alejandre Alcazar7Stefanie Endesfelder8Marius A. Möbius9Mario Rüdiger10Ursula Felderhoff-Müser11Ivo Bendix12Department of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyDepartment of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyDepartment of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyDepartment of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyDepartment of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyDepartment of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyInstitute for Lung Health (ILH), Cardiopulmonary Institute (CPI), Member of the German Centre for Lung Research, University of Giessen and Marburg Lung Center, 35392 Giessen, GermanyInstitute for Lung Health (ILH), Cardiopulmonary Institute (CPI), Member of the German Centre for Lung Research, University of Giessen and Marburg Lung Center, 35392 Giessen, GermanyDepartment of Neonatology, Charité-Universitätsmedizin Berlin, 13353 Berlin, GermanyDepartment for Neonatology and Pediatric Intensive Care, Clinic for Pediatric and Adolescence Medicine, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, GermanyDepartment for Neonatology and Pediatric Intensive Care, Clinic for Pediatric and Adolescence Medicine, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, GermanyDepartment of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyDepartment of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, Centre for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital Essen, University Duisburg-Essen, 45147 Essen, GermanyDespite improved neonatal intensive care, the risk of premature-born infants developing bronchopulmonary dysplasia (BPD) and encephalopathy of prematurity (EoP) remains high. With hyperoxia being a major underlying factor, both preterm-birth-related complications are suggested to be closely interrelated. However, experimental models are lacking for the assessment of the potentially close interplay between both organs. To establish a model, suitable for the assessment of both affected organs, Wistar rats were exposed to 80% oxygen from postnatal day 2 (P2) for seven days. Brain and lung tissues were analysed via histomorphometry, immunohistochemistry, real-time PCR, and western blot at term P11. In the brain, hyperoxia induced significant hypomyelination accompanied by a reduction in oligodendrocytes and CD68 expression on microglia cells. These changes correlate with arrested alveolarisation and an increased number of macrophages in the lung. Interestingly, in contrast to the reduced formation of pulmonary microvessels, an increased vascular density was detected in the brain. Seven days of hyperoxia induces typical characteristics of BPD and EoP in neonatal rats, thereby linking impaired alveolarisation with disturbed myelination in the brain and providing an experimental model for understanding pathophysiological mechanisms and identifying organ-spanning novel therapeutic interventions targeting both diseases.https://www.mdpi.com/2073-4409/14/6/443hyperoxia-mediated lung and brain injurypreterm birthencephalopathy of prematurity (EoP)bronchopulmonary dysplasia (BPD)myelinationvascularisation |
| spellingShingle | Stefanie Obst Meray Serdar Josephine Herz Karina Kempe Meriem Assili Mandana Rizazad Dharmesh Hirani Miguel A. Alejandre Alcazar Stefanie Endesfelder Marius A. Möbius Mario Rüdiger Ursula Felderhoff-Müser Ivo Bendix A Novel Model for Simultaneous Evaluation of Hyperoxia-Mediated Brain and Lung Injury in Neonatal Rats Cells hyperoxia-mediated lung and brain injury preterm birth encephalopathy of prematurity (EoP) bronchopulmonary dysplasia (BPD) myelination vascularisation |
| title | A Novel Model for Simultaneous Evaluation of Hyperoxia-Mediated Brain and Lung Injury in Neonatal Rats |
| title_full | A Novel Model for Simultaneous Evaluation of Hyperoxia-Mediated Brain and Lung Injury in Neonatal Rats |
| title_fullStr | A Novel Model for Simultaneous Evaluation of Hyperoxia-Mediated Brain and Lung Injury in Neonatal Rats |
| title_full_unstemmed | A Novel Model for Simultaneous Evaluation of Hyperoxia-Mediated Brain and Lung Injury in Neonatal Rats |
| title_short | A Novel Model for Simultaneous Evaluation of Hyperoxia-Mediated Brain and Lung Injury in Neonatal Rats |
| title_sort | novel model for simultaneous evaluation of hyperoxia mediated brain and lung injury in neonatal rats |
| topic | hyperoxia-mediated lung and brain injury preterm birth encephalopathy of prematurity (EoP) bronchopulmonary dysplasia (BPD) myelination vascularisation |
| url | https://www.mdpi.com/2073-4409/14/6/443 |
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