title: Effects of antenatal lipopolysaccharide and postnatal hyperoxia on airway reactivity and remodeling in a neonatal mouse model.
abstract: BACKGROUND
  Antenatal inflammation and preterm birth are associated with the development of airway diseases such as wheezing and asthma. Utilizing a newborn mouse model, we assessed the effects of maternal inflammation and postnatal hyperoxia on the neonatal airway.
  
  
  METHODS
  Pregnant C57/Bl6 dams were injected with lipopolysaccharide (LPS) or saline on embryonic day 16. Offspring were placed in room air or hyperoxia (50% O2) for 7 d and then returned to normoxia. Airway mechanics, histology, and laser capture micro-dissection (LCM) were performed.
  
  
  RESULTS
  At postnatal day 21, maternal LPS- and 50% O2-exposed pups exhibited increased resistance and decreased compliance compared to 21% O2 pups; however their effects were not synergistic. LPS and hyperoxia each increased the thickness of airway smooth muscle (ASM), but not the airway epithelial layer. Structural changes were largely limited to the conducting airways. Upregulation of inflammatory markers in the lung was observed at birth. LCM revealed increased collagen-3, transforming growth factor β, and connective tissue growth factor expression with LPS and hyperoxia within the ASM layer.
  
  
  CONCLUSIONS
  These novel studies provide functional, structural, and molecular evidence that antenatal inflammation is detrimental to the developing airway. Exposure to moderate hyperoxia does not exacerbate LPS effects on the airway.
authors.affiliation: Department of Obstetrics, and Gynecology, Division of Maternal-Fetal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Arij
authors.initials: A
authors.lastname: Faksh
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Britt
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Vogel
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ine
authors.initials: I
authors.lastname: Kuipers
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Thompson
authors.affiliation: Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Gary C
authors.initials: GC
authors.lastname: Sieck
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Pabelick
authors.affiliation: Department of Pediatrics, Division of Neonatology, Rainbow Babies Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Y S
authors.initials: YS
authors.lastname: Prakash
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D003094:Collagen / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000737:chemistry; D005260:Female; D018496:Hyperoxia / Q000503:physiopathology*; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000737:chemistry*; D008168:Lung / Q000378:metabolism; D016210:Methacholine Chloride / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000737:chemistry; D011247:Pregnancy; D011270:Pregnancy, Animal; D012119:Respiration; D012137:Respiratory System / Q000503:physiopathology*
chemical_list: D008070:Lipopolysaccharides; D016210:Methacholine Chloride; D003094:Collagen; D004549:Elastin; D010100:Oxygen