Bronchopulmonary dysplasia in a double-hit mouse model induced by intrauterine hypoxia and postnatal hyperoxia: Closer to clinical features?

Gortner, Ludwig; Monz, Dominik; Mildau, Céline; Shen, Jie; Kasoha, Mariz; Laschke, Matthias W.; Roolfs, Torge; Schmiedl, Andreas; Meier, Carola; Tutdibi, Erol

doi:10.1016/j.aanat.2013.02.010

Cited by 22 publications

(33 citation statements)

References 44 publications

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“…However, a significantly lower lung volume compared to controls was determined. Using the same mouse model, Gortner et al likewise found no morphological retardation of lung development immediately at the end of hypoxia on gestational day (gd) 18.0, but a significantly lower body weight [35], which still remained on postnatal day 1 [25]. Thus, our Hypo/No model indicates significant growth restriction without alterations in lung architecture.…”

Section: Discussionsupporting

confidence: 55%

“…The heart lung block was immediately removed and the lungs were fixed with 1% paraformaldehyde + 1% glutaraldehyde in 0.1 M cacodylate buffer by tracheal instillation with a pressure of 20 cm liquid column using an instillation device as described before [25,36]. After fixation connective tissue and the heart were removed and the volume of the lungs was determined according to the fluid displacement method [37,38].…”

Section: Methodsmentioning

confidence: 99%

“…Sampling and processing of the lungs were carried out as described elsewhere [25,38,39]. Briefly, each lung was embedded in 2% aqueous agar—agar (Merck, Darmstadt, Germany) and cut from apex to base into parallel slices with a thickness of 2 mm using a tissue slicer.…”

Section: Methodsmentioning

confidence: 99%

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Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice

Schmiedl¹,

Roolfs²,

Tutdibi³

et al. 2017

PLoS ONE

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BackgroundOxygen supply as a lifesaving intervention is frequently used to treat preterm infants suffering additionally from possible prenatal or perinatal pathogen features. The impact of oxygen and/or physical lung injury may influence the morphological lung development, leading to a chronic postnatal lung disease called bronchopulmonary dysplasia (BPD). At present different experimental BPD models are used. However, there are no systematic comparative studies regarding different influences of oxygen on morphological lung maturation.ObjectiveWe investigated the influence of prenatal hypoxia and/or postnatal hyperoxia on morphological lung maturation based on stereological parameters, to find out which model best reflects morphological changes in lung development comparable with alterations found in BPD.MethodsPregnant mice were exposed to normoxia, the offspring to normoxia (No/No) or to hyperoxia (No/Hyper). Furthermore, pregnant mice were exposed to hypoxia and the offspring to normoxia (Hypo/No) or to hyperoxia (Hypo/Hyper). Stereological investigations were performed on all pups at 14 days after birth.ResultsCompared to controls (No/No) 1) the lung volume was significantly reduced in the No/Hyper and Hypo/Hyper groups, 2) the volume weighted mean volume of the parenchymal airspaces was significantly higher in the Hypo/Hyper group, 3) the total air space volume was significantly lower in the No/Hyper and Hypo/Hyper groups, 4) the total septal surface showed significantly lower values in the No/Hyper and Hypo/Hyper groups, 5) the wall thickness of septa showed the highest values in the Hypo/Hyper group without reaching significance, 6) the volume density and the volume weighted mean volume of lamellar bodies in alveolar epithelial cells type II (AEII) were significantly lower in the Hypo/Hyper group.ConclusionPrenatal hypoxia and postnatal hyperoxia differentially influence the maturation of lung parenchyma. In 14 day old mice a significant retardation of morphological lung development leading to BPD-like alterations indicated by different parameters was only seen after hypoxia and hyperoxia.

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Section: Discussionsupporting

confidence: 55%

Section: Methodsmentioning

confidence: 99%

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Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice

Schmiedl¹,

Roolfs²,

Tutdibi³

et al. 2017

PLoS ONE

Self Cite

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“…In addition to producing a histological picture of BPD with decreased alveolar septation and simplified terminal airway structures, this model also leads to significant growth restriction by PN day 14, as represented by decreased total body length and weight and decreased lung and brain weight. Compared with mice exposed to prenatal normoxia, the prenatal hypoxia mice were born at decreased weight, which mimics intrauterine growth restriction seen in many preterm infants (31). Mice in the "double-hit" model subsequently treated with umbilical cord mononuclear cells at PN day 7 showed decreased inflammatory markers such as IL-1␤ compared with untreated double-hit mice and normalization of alveolar septal thickness compared with normoxic controls (57).…”

Section: Rodent Models Of Pulmonary Diseasementioning

confidence: 96%

Animal models of bronchopulmonary dysplasia. The term mouse models

Berger

Bhandari

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

214

168

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Berger J, Bhandari V. Animal models of bronchopulmonary dysplasia. I. The term mouse models. Am J Physiol Lung Cell Mol Physiol 307: L936 -L947, 2014. First published October 10, 2014 doi:10.1152/ajplung.00159.2014.-The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante-and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.

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“…Increase in the survival rate of premature infants can be attributed to progress in mechanical ventilation techniques, application of exogenous surfactants and glucocorticoids, and improvements in nutritional support and nursing. However, the incidence rate of BPD continues to rise annually, which seriously affects the survival and quality of life of newborns (Gortner et al, 2013). Currently, BPD is pathologically typified by alveolar and pulmonary vascular dysplasias.…”

Section: Introductionmentioning

confidence: 99%

Expression of transforming growth factor-β1 in neonatal rats with hyperoxia-induced bronchopulmonary dysplasia and its relationship with lung development

Yan

Zhong

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to detect the expression of transforming growth factor-b1 (TGF-b1) in neonatal rats with hyperoxia-induced bronchopulmonary dysplasia (BPD) and to explore its relationship with lung development. Forty-eight rats (2-3 days old) were randomly divided into a hyperoxia group and a control group (N = 24) which were then fed in ≥95% oxygen atmosphere and air, respectively. On the 1st, 3rd and 7th days of hyperoxia exposure, morphological changes of lung tissues were observed under an optical microscope. TGF-b1 mRNA and protein levels in lung tissues were detected by real-time quantitative polymerase chain reaction and western blot, respectively. With increasing time of hyperoxia exposure, the hyperoxia group gradually suffered from pathological changes such as poor development of lung tissues, alveolar simplification, decrease in the number of alveoli, and hindered pulmonary microvascular development. On the 7th day of hyperoxia exposure, TGF-b1 mRNA and protein levels (relative to b-actin) of the hyperoxia group (0.34 ± 0.19 and 0.21 ± 0.09, respectively) were significantly lower than those of the control group (0.83 ± 0.45 and 0.57 ± 0.45, respectively; P < 0.05). TGF-b1 participates in the pathogenesis of BPD as an important regulatory factor during pulmonary vascular development.

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Bronchopulmonary dysplasia in a double-hit mouse model induced by intrauterine hypoxia and postnatal hyperoxia: Closer to clinical features?

Cited by 22 publications

References 44 publications

Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice

Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice

Animal models of bronchopulmonary dysplasia. The term mouse models

Expression of transforming growth factor-β1 in neonatal rats with hyperoxia-induced bronchopulmonary dysplasia and its relationship with lung development

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