Prolonged Exposure to Neonatal Hyperoxia Impairs Neuronal and Oligodendrocyte Maturation Associated with Long-Lasting Neuroinflammatory Responses in Juvenile Mice
Stefanie Obst,
Meray Serdar,
Karina Kempe,
Dharmesh Hirani,
Ursula Felderhoff-Müser,
Josephine Herz,
Miguel A. Alejandre Alcazar,
Ivo Bendix
Affiliations
Stefanie Obst
Department 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, Germany
Meray Serdar
Department 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, Germany
Karina Kempe
Department 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, Germany
Dharmesh Hirani
Institute for Lung Health (ILH), Cardiopulmonary Institute (CPI), Member of the German Centre for Lung Research, University of Giessen and Marburg Lung Center, 35392 Giessen, Germany
Ursula Felderhoff-Müser
Department 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, Germany
Josephine Herz
Department 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, Germany
Miguel A. Alejandre Alcazar
Institute for Lung Health (ILH), Cardiopulmonary Institute (CPI), Member of the German Centre for Lung Research, University of Giessen and Marburg Lung Center, 35392 Giessen, Germany
Ivo Bendix
Department 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, Germany
Preterm infants often require oxygen supplementation, resulting in high risk for bronchopulmonary dysplasia (BPD) and neurodevelopmental deficits. Despite a growing number of studies, there is still little knowledge about brain injury in BPD models. Therefore, we exposed neonatal C57BL/6 mice to 85% oxygen from birth to postnatal day (P) 14. At P28, two weeks after recovery under normoxic conditions, right hemisphere was used for the analysis of mRNA and the left hemisphere for protein expression of neuronal cells, neuroinflammatory and vascularisation markers, analysed by real-time PCR and Western blot, respectively. Hyperoxia led to an altered expression of markers associated with neuronal and oligodendrocyte maturation and neuroinflammation such as Dcx, Nestin, Il-1β, Il-6, NG2, and YM1/2. These changes were accompanied by an increased expression of genes involved in angiogenesis and vascular remodelling, e.g., Vegf-a, Nrp-1, and Icam-1. Together, 14 days of hyperoxia triggered a phenotypic response, resembling signs of encephalopathy of prematurity (EoP).
