Effects of Postnatal Dexamethasone or Hydrocortisone in a Rat Model of Antenatal Lipopolysaccharide and Neonatal Hyperoxia Exposure

Abstract

The aim of our study was to investigate the differential effects of dexamethasone (DXM) and hydrocortisone (HCS) on somatic growth and postnatal lung development in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was induced by administering intra-amniotic lipopolysaccharide (LPS) and postnatal hyperoxia. The rats were treated with a 6-day (D1-D6) tapering course of DXM (starting dose 0.5 mg/kg/day), HCS (starting dose 2 mg/kg/day), or an equivalent volume of normal saline. DXM treatment in a rat model of BPD induced by LPS and hyperoxia was also associated with a more profound weight loss compared to control and LPS + O2 groups not exposed to corticosteroid, whereas HCS treatment affected body weight only slightly. Examination of lung morphology showed worse mean cord length in both LPS + O2 + DXM and LPS + O2 + HCS groups as compared to the LPS + O2 alone group, and the LPS + O2 + DXM group had thicker alveolar walls than the LPS + O2 group at day 14. The HCS treatment was not significantly associated with aberrant alveolar wall thickening and retarded somatic growth. The use of postnatal DXM or HCS in a rat model of BPD induced by intra-amniotic LPS and postnatal hyperoxia appeared detrimental to lung growth, but there was less effect in the case of HCS. These findings suggest that effect of HCS on somatic growth and pulmonary outcome may be better tolerated in neonates for preventing and/or treating BPD.

Dose-dependent effects of glucocorticoids on pulmonary vascular development in a murine model of hyperoxic lung injury

“…To evaluate the effects of oxygen and HC exposure on alveolar growth, mean alveolar area and mean chord length were measured in hematoxylin-stained lung sections. Similar to previous reports ( 10 , 22 ), hyperoxia exposure increased both mean alveolar area and mean chord length (137±3% and 128±4% respectively vs. normoxia-vehicle) ( Figure 3 ). Alveolar simplification was worsened in hyperoxic animals treated with 10 mg/kg HC but was not significantly affected by lower HC doses ( Figures 3 and 4 ).…”

“…This was evidenced in our model as demonstrated by increased mean alveolar area and chord length in animals exposed to chronic hyperoxia ( Figure 3 ) ( 24 ). Glucocorticoids alone have been known to adversely affect alveolar growth, with HC being reported as less detrimental compared to dexamethasone ( 22 , 32 ). In our study, we observed dose-dependent effects of HC on alveolar growth with worsening alveolar simplification associated with increasing HC doses during hyperoxia exposure ( Figures 3 and 4 ).…”

Rosiglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, Restores Alveolar and Pulmonary Vascular Development in a Rat Model of Bronchopulmonary Dysplasia

“…In our previous studies, intra-amniotic LPS and subsequent postnatal hyperoxia caused an arrest in alveolar and pulmonary vascular development, which is the hallmark of BPD, in a newborn rat model 10,11,13,14. In the present study, the RGZ treatment was found to preserve alveolar and pulmonary vascular development against the detrimental influence of intra-amniotic inflammation and postnatal hyperoxia.…”

“…The newborn rat pups which were exposed to intra-amniotic LPS were then exposed to 80% O 2 in a Plexiglas chamber with adaptors to supply and vent gas (BPD groups), and pups which were exposed to vehicle were kept in room air (No BPD groups) with their dams for 7 days beginning on the day of birth (P1), as previously described. 10 To the newborn rat pups in the BPD groups, 80% O 2 was constantly administered using mass flow controllers (TSC-220; MFC Korea, Suwon, Korea). Nursing rat dams were switched between 80% O 2 and air every 24 hour to avoid oxygen toxicity.…”

Bronchopulmonary Dysplasia: Crosstalk Between PPARγ, WNT/β-Catenin and TGF-β Pathways; The Potential Therapeutic Role of PPARγ Agonists

“…Neonatal resuscitation of premature infants between 24 and 26 weeks (canalicular stage) with 30% O2 instead of 90% O2 decreases the incidence of BDP at 36 weeks by a factor of about 2 (46). In a newborn rat model of BPD induced by intra-amniotic LPS administration and postnatal hyperoxia, there is an arrest in alveolar and pulmonary vascular development, which is a hallmark of BPD (47–50). Hyperoxia-induced neonatal lung injury is associated with activation of Wnt/β-catenin signaling and inhibition of WNT/β-catenin signaling attenuates hyperoxia-induced pulmonary hypertension in neonatal rats (51, 52).…”