PMID- 35251477 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20220324 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2022 DP - 2022 TI - Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis. PG - 5784146 LID - 10.1155/2022/5784146 [doi] LID - 5784146 AB - Approximately 11.1% of all newborns worldwide are born preterm. Improved neonatal intensive care significantly increased survival rates over the last decades but failed to reduce the risk for the development of chronic lung disease (i.e., bronchopulmonary dysplasia (BPD)) and impaired neurodevelopment (i.e., encephalopathy of prematurity (EoP)), two major long-term sequelae of prematurity. Premature infants are exposed to relative hyperoxia, when compared to physiological in-utero conditions and, if needed to additional therapeutic oxygen supplementation. Both are associated with an increased risk for impaired organ development. Since the detrimental effects of hyperoxia on the immature retina are known for many years, lung and brain have come into focus in the last decade. Hyperoxia-induced excessive production of reactive oxygen species leading to oxidative stress and inflammation contribute to pulmonary growth restriction and abnormal neurodevelopment, including myelination deficits. Despite a large body of studies, which unraveled important pathophysiological mechanisms for both organs at risk, the majority focused exclusively either on lung or on brain injury. However, considering that preterm infants suffering from BPD are at higher risk for poor neurodevelopmental outcome, an interaction between both organs seems plausible. This review summarizes recent findings regarding mechanisms of hyperoxia-induced neonatal lung and brain injury. We will discuss common pathophysiological pathways, which potentially link both injured organ systems. Furthermore, promises and needs of currently suggested therapies, including pharmacological and regenerative cell-based treatments for BPD and EoP, will be emphasized. Limited therapeutic approaches highlight the urgent need for a better understanding of the mechanisms underlying detrimental effects of hyperoxia on the lung-brain axis in order to pave the way for the development of novel multimodal therapies, ideally targeting both severe preterm birth-associated complications. CI - Copyright (c) 2022 Stefanie Obst et al. FAU - Obst, Stefanie AU - Obst S AUID- ORCID: 0000-0002-9797-1262 AD - Department of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. AD - Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University Duisburg-Essen, 45147 Essen, Germany. FAU - Herz, Josephine AU - Herz J AUID- ORCID: 0000-0001-8132-7459 AD - Department of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. AD - Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University Duisburg-Essen, 45147 Essen, Germany. FAU - Alejandre Alcazar, Miguel A AU - Alejandre Alcazar MA AUID- ORCID: 0000-0002-3176-0411 AD - Cologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Faculty of Medicine, University of Cologne, 50931 Cologne, Germany. AD - Institute for Lung Health, Member of the German Centre for Lung Research, University of Giessen and Marburg Lung Center, 35392 Giessen, Germany. AD - Department of Pediatric and Adolescent Medicine, University of Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, Germany. FAU - Endesfelder, Stefanie AU - Endesfelder S AUID- ORCID: 0000-0002-4030-7969 AD - Department of Neonatology, Charite-Universitatsmedizin Berlin, 13353 Berlin, Germany. FAU - Mobius, Marius A AU - Mobius MA AUID- ORCID: 0000-0002-8811-8454 AD - Department for Neonatology and Pediatric Intensive Care, Clinic for Pediatric and Adolescence Medicine, Faculty of Medicine, Technische Universitat Dresden, 01307 Dresden, Germany. AD - Saxony Center for Feto-Neonatal Health, Faculty of Medicine, Technische Universitat Dresden, 01307 Dresden, Germany. FAU - Rudiger, Mario AU - Rudiger M AUID- ORCID: 0000-0001-7498-1209 AD - Department for Neonatology and Pediatric Intensive Care, Clinic for Pediatric and Adolescence Medicine, Faculty of Medicine, Technische Universitat Dresden, 01307 Dresden, Germany. AD - Saxony Center for Feto-Neonatal Health, Faculty of Medicine, Technische Universitat Dresden, 01307 Dresden, Germany. FAU - Felderhoff-Muser, Ursula AU - Felderhoff-Muser U AUID- ORCID: 0000-0002-7765-8893 AD - Department of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. AD - Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University Duisburg-Essen, 45147 Essen, Germany. FAU - Bendix, Ivo AU - Bendix I AUID- ORCID: 0000-0002-9751-3640 AD - Department of Paediatrics I, Neonatology and Experimental Perinatal Neurosciences, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany. AD - Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University Duisburg-Essen, 45147 Essen, Germany. LA - eng PT - Journal Article PT - Review DEP - 20220224 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Reactive Oxygen Species) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Animals, Newborn MH - Brain Injuries/*etiology/*metabolism MH - Bronchopulmonary Dysplasia/*etiology/*metabolism MH - Disease Models, Animal MH - Female MH - Humans MH - Hyperoxia/*complications MH - Infant, Newborn MH - *Infant, Premature MH - *Oxidative Stress MH - Oxygen/metabolism MH - Pregnancy MH - Premature Birth MH - Reactive Oxygen Species/metabolism MH - Signal Transduction PMC - PMC8894035 COIS- MAM is founder and coowner of MDTB Cells GmbH, a spin-off company from the Technische Universitat Dresden producing mesenchymal cells for clinical and laboratory purposes. MR and MAM are coinventors of granted patent DE102016114043 and pending patents US20190185809, CA3031048, EP34911113, and WO2018020008, which are all property of MDTB Cells GmbH. All authors declare that there is no conflict of interest regarding the publication of this paper. EDAT- 2022/03/08 06:00 MHDA- 2022/03/25 06:00 PMCR- 2022/02/24 CRDT- 2022/03/07 06:04 PHST- 2021/11/25 00:00 [received] PHST- 2022/01/04 00:00 [accepted] PHST- 2022/03/07 06:04 [entrez] PHST- 2022/03/08 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2022/02/24 00:00 [pmc-release] AID - 10.1155/2022/5784146 [doi] PST - epublish SO - Oxid Med Cell Longev. 2022 Feb 24;2022:5784146. doi: 10.1155/2022/5784146. eCollection 2022.