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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

In utero, the fetus and its lungs develop in a hypoxic environment, where HIF-1α and VEGFA signaling constitute major determinants of further development. Disruption of this homeostasis after preterm delivery and extrauterine exposure to high fractions of oxygen are among the key events leading to bronchopulmonary dysplasia (BPD). Reactive oxygen species (ROS) production constitutes the initial driver of pulmonary inflammation and cell death, altered gene expression, and vasoconstriction, leading to the distortion of further lung development. From preclinical studies mainly performed on rodents over the past two decades, the deleterious effects of oxygen toxicity and the injurious insults and downstream cascades arising from ROS production are well recognized. This article provides a concise overview of disease drivers and different therapeutic approaches that have been successfully tested within experimental models. Despite current studies, clinical researchers are still faced with an unmet clinical need, and many of these strategies have not proven to be equally effective in clinical trials. In light of this challenge, adapting experimental models to the complexity of the clinical situation and pursuing new directions constitute appropriate actions to overcome this dilemma. Our review intends to stimulate research activities towards the understanding of an important issue of immature lung injury.

Details

Title
Oxygen Toxicity to the Immature Lung—Part I: Pathomechanistic Understanding and Preclinical Perspectives
Author
Choi, Yesi 1   VIAFID ORCID Logo  ; Rekers, Lisa 1 ; Dong, Ying 2 ; Holzfurtner, Lena 1 ; Goetz, Maurizio J 1 ; Shahzad, Tayyab 1 ; Zimmer, Klaus-Peter 1 ; Behnke, Judith 1   VIAFID ORCID Logo  ; Behnke, Jonas 3 ; Bellusci, Saverio 4 ; Ehrhardt, Harald 1   VIAFID ORCID Logo 

 Department of General Pediatrics and Neonatology, Justus-Liebig-University, Universities of Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany; [email protected] (Y.C.); [email protected] (L.R.); [email protected] (Y.D.); [email protected] (L.H.); [email protected] (M.J.G.); [email protected] (T.S.); [email protected] (K.-P.Z.); [email protected] (J.B.) 
 Department of General Pediatrics and Neonatology, Justus-Liebig-University, Universities of Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany; [email protected] (Y.C.); [email protected] (L.R.); [email protected] (Y.D.); [email protected] (L.H.); [email protected] (M.J.G.); [email protected] (T.S.); [email protected] (K.-P.Z.); [email protected] (J.B.); Department of Internal Medicine II, Universities of Giessen and Marburg Lung Center (UGMLC), Cardiopulmonary Institute (CPI), 35392 Giessen, Germany; [email protected] 
 Department of Internal Medicine V, Justus-Liebig-University, Universities of Giessen and Marburg Lung Center (UGMLC), 35392 Giessen, Germany; [email protected] 
 Department of Internal Medicine II, Universities of Giessen and Marburg Lung Center (UGMLC), Cardiopulmonary Institute (CPI), 35392 Giessen, Germany; [email protected] 
First page
11006
Publication year
2021
Publication date
2021
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2584429687
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.