Obst Stefanie, Serdar Meray, Herz Josephine, Kempe Karina, Assili Meriem, Rizazad Mandana, Hirani Dharmesh, Alejandre Alcazar Miguel A, Endesfelder Stefanie, Möbius Marius A, Rüdiger Mario, Felderhoff-Müser Ursula, Bendix Ivo
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.
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.
Cells. 2025 Mar 16;14(6):443. doi: 10.3390/cells14060443.
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.
尽管新生儿重症监护有所改善，但早产婴儿患支气管肺发育不良（BPD）和早产脑病（EoP）的风险仍然很高。由于高氧是一个主要潜在因素，这两种早产相关并发症被认为密切相关。然而，目前缺乏用于评估这两个器官之间潜在密切相互作用的实验模型。为了建立一个适用于评估两个受影响器官的模型，将Wistar大鼠从出生后第2天（P2）开始暴露于80%氧气中，持续7天。在足月P11时，通过组织形态计量学、免疫组织化学、实时PCR和蛋白质免疫印迹法对脑和肺组织进行分析。在脑中，高氧诱导显著的髓鞘形成不足，伴有少突胶质细胞减少和小胶质细胞上CD68表达降低。这些变化与肺泡化停滞和肺中巨噬细胞数量增加相关。有趣的是，与肺微血管形成减少相反，在脑中检测到血管密度增加。7天高氧诱导新生大鼠出现BPD和EoP的典型特征，从而将肺泡化受损与脑髓鞘形成紊乱联系起来，并为理解病理生理机制和确定针对这两种疾病的跨器官新型治疗干预措施提供了一个实验模型。
