Recovery of airway structure and function after hyperoxic exposure in immature rats.

Hershenson, Marc B.; Abe, Mark K.; Kelleher, Michael D.; Naureckas, Edward T.; Garland, Allan; Zimmermann, Anne; Rubinstein, Valeria J.; Solway, Julian

doi:10.1164/ajrccm.149.6.8004327

Cited by 26 publications

(16 citation statements)

References 19 publications

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“…Histopatholo gical analysis of both small and large airways from proximal and distal lung also failed to detect any apparent increase in airway smooth muscle mass. These results differ from those of Hershenson et al (1994), who found airway hyperreactivity in 21-day-old rat pups exposed to >95% oxygen for 7 days. They reported a correlation between the hyperoxia-induced increase in airway hyperreactivity and an accompanying increase in small and medium airway smooth muscle thickness.…”

Section: Discussioncontrasting

confidence: 99%

Hyperoxia-Induced Airway Hyperreactivity in Neonatal Guinea Pigs Is Not Inflammation Dependent

Canada

Schulman

Winsett

et al. 1998

Inhalation Toxicology

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A high percentage of neonatal human infants exposed to prolonged assisted ventilation with supplemental oxygen develop airway hyperreactivity. In order to demonstrate that this effect could be replicated in guinea pigs, 4-day-old pups were exposed either to air or 70% oxygen for 4 days. Nine days later each group was subjected to a histamine challenge and differences in respiratory mechanics were determined. The airway pressure response of the hyperoxia group was significantly greater and the respiratory compliance was significantly less than those of the air-exposed pups. The role of inflammation was assessed both by analysis of bronchoalveolar lavage fluid ( BAL) and by histopathology on animals 1 day after discontinuation of the exposures. There were no differences between the two groups in BAL protein, total cell count, or the white blood cell ( WBC) differential. Histology did not show any evidence of a difference between the two groups in inflammation or in airway remodeling.The effects of hyperoxia on the lungs of animals have been studied extensively. Acutely, concentrations of oxygen >95% result in mortality to adult animals with the time to 100% mortality being species dependent. Concentrations less than that which produces lethality also produce delayed adverse effects on the lung, including an increase in 15 Inhalation Toxicology, 10:15-25, 1998

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Section: Discussioncontrasting

confidence: 99%

Hyperoxia-Induced Airway Hyperreactivity in Neonatal Guinea Pigs Is Not Inflammation Dependent

Canada

Schulman

Winsett

et al. 1998

Inhalation Toxicology

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“…They have demonstrated both recovery of hyperoxia-induced airway remodeling 2 wk after hyperoxia exposure in rat pups and persistence of airway hyperreactivity 9 days after cessation of hyperoxic exposure in neonatal guinea pigs (7,17). Both studies employed exposure to high supplemental oxygen (Ͼ95% and 70%, respectively) and neither study used neonatal mice, confounding comparison to our own data.…”

Section: Discussionmentioning

confidence: 84%

“…From an in vivo perspective, hyperoxiaexposed neonatal rodents have been widely employed to study the pathophysiology of neonatal lung injury. Initial studies focused on the effects of ϳ95% oxygen and documented increased airway reactivity, accompanied by an increase in airway smooth muscle (ASM) layer thickness, both of which resolved several days after cessation of oxygen exposure (7). In contrast, neonatal guinea pigs exposed to 70% oxygen showed a persistent increase in airway response to cholinergic agonist after return to normoxia (17).…”

mentioning

confidence: 99%

Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway

Wang

Jafri

Martin

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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MacFarlane PM. Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway. Am J Physiol Lung Cell Mol Physiol 307: L295-L301, 2014. First published June 20, 2014 doi:10.1152/ajplung.00208.2013.-Wheezing is a major long-term respiratory morbidity in preterm infants with and without bronchopulmonary dysplasia. We hypothesized that mild vs. severe hyperoxic exposure in neonatal mice differentially affects airway smooth muscle hypertrophy and resultant airway reactivity. Newborn mice were exposed to 7 days of mild (40% oxygen) or severe (70% oxygen) hyperoxia vs. room air controls. Respiratory system resistance (Rrs), compliance (Crs), and airway reactivity were measured 14 days after oxygen exposure ended under ketamine/ xylazine anesthesia. Baseline Rrs increased and Crs decreased in both treatment groups. Methacholine challenge dose dependently increased Rrs and decreased Crs in 40% oxygen-exposed mice, whereas Rrs and Crs responses were similar between 70% oxygen-exposed and normoxic controls. Airway smooth muscle thickness was increased in 40%-but not 70%-exposed mice, whereas collagen increased and both alveolar number and radial alveolar counts decreased after 40% and 70% oxygen. These data indicate that severity of hyperoxia may differentially affect structural and functional changes in the developing mouse airway that contribute to longer-term hyperreactivity. These findings may be important to our understanding of the complex role of neonatal supplemental oxygen therapy in postnatal development of airway responsiveness.

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“…bronchial smooth muscle; oxygen; hyperoxia; brain-derived neurotrophic factor; tropomyosin related kinase; calcium; substance P PRETERM BIRTH AND NEONATAL lung injury are associated with bronchopulmonary dysplasia (BPD) and a high incidence of childhood asthma (1, 21). While BPD is likely multifactorial in origin, a well-characterized model for BPD is neonatal hyperoxic exposure in rat pups, which is associated with increased cholinergically mediated airway contractile responses in vitro and in vivo (6,24,59). In this regard, neurally mediated bronchoconstriction involves cholinergic mechanisms as well as nonadrenergic/noncholinergic (NANC) pathways (9, 44, 55) mediated via subepithelial C-fiber sensory afferents that release tachykinins [neurokinin A and B and substance P (SP) (19)].…”

mentioning

confidence: 99%

Neurokinin-neurotrophin interactions in airway smooth muscle

Meuchel¹,

Stewart

Smelter

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Neurally derived tachykinins such as substance P (SP) play a key role in modulating airway contractility (especially with inflammation). Separately, the neurotrophin brain-derived neurotrophic factor (BDNF; potentially derived from nerves as well as airway smooth muscle; ASM) and its tropomyosin-related kinase receptor, TrkB, are involved in enhanced airway contractility. In this study, we hypothesized that neurokinins and neurotrophins are linked in enhancing intracellular Ca(2+) concentration ([Ca(2+)](i)) regulation in ASM. In rat ASM cells, 24 h exposure to 10 nM SP significantly increased BDNF and TrkB expression (P < 0.05). Furthermore, [Ca(2+)](i) responses to 1 μM ACh as well as BDNF (30 min) effects on [Ca(2+)](i) regulation were enhanced by prior SP exposure, largely via increased Ca(2+) influx (P < 0.05). The enhancing effect of SP on BDNF signaling was blunted by the neurokinin-2 receptor antagonist MEN-10376 (1 μM, P < 0.05) to a greater extent than the neurokinin-1 receptor antagonist RP-67580 (5 nM). Chelation of extracellular BDNF (chimeric TrkB-F(c); 1 μg/ml), as well as tyrosine kinase inhibition (100 nM K252a), substantially blunted SP effects (P < 0.05). Overnight (24 h) exposure of ASM cells to 50% oxygen increased BDNF and TrkB expression and potentiated both SP- and BDNF-induced enhancement of [Ca(2+)](i) (P < 0.05). These results suggest a novel interaction between SP and BDNF in regulating agonist-induced [Ca(2+)](i) regulation in ASM. The autocrine mechanism we present here represents a new area in the development of bronchoconstrictive reflex response and airway hyperreactive disorders.

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Recovery of airway structure and function after hyperoxic exposure in immature rats.

Cited by 26 publications

References 19 publications

Hyperoxia-Induced Airway Hyperreactivity in Neonatal Guinea Pigs Is Not Inflammation Dependent

Hyperoxia-Induced Airway Hyperreactivity in Neonatal Guinea Pigs Is Not Inflammation Dependent

Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway

Neurokinin-neurotrophin interactions in airway smooth muscle

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