Oral Maternal Administration of the Cytochrome P450 (CYP)1A/1B Inducer, Beta-Napthoflavone (BNF), Attenuates Oxygen-Mediated Lung Injury in Newborn Mice: Implications for Bronchopulmonary Dysplasia (BPD)

Author(s):  
X. Couroucli ◽  
Y.W. Liang ◽  
K. Lingappan ◽  
P. Maturu ◽  
W. Jiang ◽  
...  
2020 ◽  
Vol 19 (1) ◽  
pp. 120-126
Author(s):  
Ayinuerguli Adili ◽  
Adilijiang Kari ◽  
Chuanlong Song ◽  
Abulaiti Abuduhaer

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.


Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 132
Author(s):  
Vikramaditya Dumpa ◽  
Vineet Bhandari

Recent advances in neonatology have led to the increased survival of extremely low-birth weight infants. However, the incidence of bronchopulmonary dysplasia (BPD) has not improved proportionally, partly due to increased survival of extremely premature infants born at the late-canalicular stage of lung development. Due to minimal surfactant production at this stage, these infants are at risk for severe respiratory distress syndrome, needing prolonged ventilation. While the etiology of BPD is multifactorial with antenatal, postnatal, and genetic factors playing a role, ventilator-induced lung injury is a major, potentially modifiable, risk factor implicated in its causation. Infants with BPD are at a higher risk of developing complications including sepsis, pulmonary arterial hypertension, respiratory failure, and death. Long-term problems include increased risk of hospital readmissions, respiratory infections, and asthma-like symptoms during infancy and childhood. Survivors who have BPD are also at increased risk of poor neurodevelopmental outcomes. While the ultimate solution for avoiding BPD lies in the prevention of preterm births, strategies to decrease its incidence are the need of the hour. It is time to focus on gentler modes of ventilation and the use of less invasive surfactant administration techniques to mitigate lung injury, thereby potentially decreasing the burden of BPD. In this article, we discuss the use of non-invasive ventilation in premature infants, with an emphasis on studies showing an effect on BPD with different modes of non-invasive ventilation. Practical considerations in the use of nasal intermittent positive pressure ventilation are also discussed, considering the significant heterogeneity in clinical practices and management strategies in its use.


2014 ◽  
Vol 307 (12) ◽  
pp. L936-L947 ◽  
Author(s):  
Jessica Berger ◽  
Vineet Bhandari

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.


2012 ◽  
Vol 211 ◽  
pp. S163
Author(s):  
Xanthi Couroucli ◽  
Yanhong Liang ◽  
Lihua Wang ◽  
Weiwu Jiang ◽  
Bhagavatula Moorthy

2016 ◽  
Vol 33 (11) ◽  
pp. 1076-1078 ◽  
Author(s):  
Alan Jobe

Although bronchopulmonary dysplasia (BPD) is the most frequent adverse outcome for infants born at < 30 weeks gestational age, there remain major gaps in understanding the pathophysiology, and thus there are few effective targeted therapies to prevent and treat BPD. This review will focus on the substantial problems and knowledge gaps for the clinician and investigator when considering lung injury and BPD. The epidemiology of BPD is clear: BPD is a lung injury syndrome predominantly in extremely low-birth-weight infants with an incidence that increases as gestation/birth weight decrease, with growth restriction, in males and with fetal exposures and with injury from postdelivery respiratory care. However, we do not have a good definition of BPD that identifies the infants that die of respiratory disease before 36 weeks or that predicts long-term outcomes as well. The injury resulting in BPD likely begins as altered lung development before delivery in many infants (small for gestational age, chorioamnionitis, tobacco exposure), can be initiated by resuscitating at birth, and then amplified by postnatal exposures (oxygen, mechanical ventilation, infection). Conceptually the events leading to BPD are the continued interplay of lung development that is altered progressively by injury and repair to result in poorly defined phenotypes of BPD. The injury pathways prominently cause inflammation, and as a proof of principle, corticosteroids can decrease the incidence and severity of BPD, as demonstrated by three recent trials of the early use of steroids. There are likely “adaptation” and “tolerance” responses that modulate the injury and repair to increase or decrease the damage, interactions that are not understood. BPD is a more complex disease.


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