RT Journal Article
SR Electronic
T1 Refinement of the hyperoxia-based experimental mouse model of bronchopulmonary dysplasia
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA4027
DO 10.1183/13993003.congress-2016.PA4027
VO 48
IS suppl 60
A1 Nardiello, Claudio
A1 Mizíková, Ivana
A1 Ruiz-Camp, Jordi
A1 Seeger, Werner
A1 Morty, Rory
YR 2016
UL https://publications.ersnet.org//content/48/suppl_60/PA4027.abstract
AB Bronchopulmonary dysplasia (BPD) is a complication of premature birth, characterized by arrested alveolarisation. Studies on BPD rely on hyperoxia-based rodent models, which lack standardisation.We aimed to assess the minimum exposure and concentration of O2 required for arrested alveolarisation. Newborn C57BL/6J mouse pups were exposed to 21%, 40%, 60% and 85% O2 for 14 days or to 85% O2 for 4 h, or 1, 7, or 14 days, when lung structure was assessed by stereology. A 40% or 60% O2 exposure reduced alveoli number from 4.20×106 (at 21% O2) to 3.55×106 (P=0.0002) or 2.99×106 (P=0.0323), respectively, without impact on septal thickness. At 85% O2, alveoli number was reduced to 1.37×106 (P<0.0001), and septal thickness was increased (from 10.00 µm to 11.96 µm, P=0.0294). An 85%-O2 exposure for the first 4 h of life followed by room air exposure reduced alveoli number from 4.20×106 to 3.35×106 (P=0.0042) and increased septal thickness (from 10.00 µm to 11.81 µm, P=0.0082). A 24-h 85% O2 exposure on day 1 reduced alveoli number at day 14 to 3.51×106 (P=0.0155), while a 7-day 85% O2 exposure dramatically decreased alveoli number to 2.11×106 (P<0.0001) by day 14; where septal thickness was increased to 12.87 µm (P<0.0001). These data - the first stereological analysis of lung alveolarisation in the BPD hyperoxia model - indicate that the alveolarisation arrest is dependent upon the O2 concentration and duration, and that the effect of the shift from 85% O2 to 21% O2 on septal thickness is dependent on this timing of the transition. These data suggest that continuous exposure of the developing mouse lung to 85% O2 for 14 days, best recapitulates both changes in alveolar number and septal thickness.