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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Intra-amniotic LPS amplifies hyperoxia-induced airway hyperreactivity in neonatal rats
Chang Won Choi1, Beyong Il Kim, Stanley N Mason
1Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, South Korea. choicw@snu.ac.kr
Insights
Intra-amniotic lipopolysaccharide (LPS) exposure amplified airway hyperreactivity (AHR) in rat pups exposed to postnatal hyperoxia. This effect was linked to increased mast cell degranulation, not altered lung morphology.
Area of Science:
- Neonatal respiratory research
- Pulmonary pharmacology
- Developmental toxicology
Background:
- Previous studies demonstrated intra-amniotic lipopolysaccharide (LPS) amplifies alveolar hypoplasia from postnatal hyperoxia.
- This study investigated if intra-amniotic LPS also amplifies hyperoxia-induced airway hyperreactivity (AHR).
Purpose of the Study:
- To determine if intra-amniotic LPS exposure exacerbates AHR in rat pups exposed to postnatal hyperoxia.
- To explore the underlying mechanisms, including mast cell degranulation and lung morphology.
Main Methods:
- Pregnant rats received intra-amniotic LPS or saline injection.
- Offspring were exposed to hyperoxia (60% O₂) or air for 14 days post-birth.
- Airway reactivity was assessed using forced oscillometry with methacholine challenge; lungs were analyzed morphologically.
Main Results:
- Postnatal hyperoxia increased airway reactivity and decreased lung compliance.
- Intra-amniotic LPS further amplified hyperoxia-induced AHR but did not worsen compliance.
- Combined LPS and hyperoxia increased mast cell degranulation in hilar airways without altering lung parenchyma or airway morphology.
Conclusions:
- Intra-amniotic LPS amplifies postnatal hyperoxia-induced AHR in a rat model.
- Increased airway mast cell degranulation is associated with this amplified AHR.
- No significant changes in lung parenchyma or airway morphology explain the augmentation of AHR by LPS.
Background:
We previously showed that intra-amniotic lipopolysaccharide (LPS) amplifies alveolar hypoplasia induced by postnatal hyperoxia. We determined whether the priming effect of intra-amniotic LPS amplifies hyperoxia-induced airway hyperreactivity (AHR).
Methods:
LPS or normal saline was injected into the amniotic cavities of pregnant rats at the 20th day of gestation. After birth, rat pups were exposed to 60% O₂ or air for 14 d. On postnatal day 14, rat pups underwent forced oscillometry, which included a challenge with nebulized methacholine, and the lungs were harvested for morphological studies.
Results:
Hyperoxia significantly increased airway reactivity and decreased compliance. Intra-amniotic LPS further increased hyperoxia-induced AHR but did not further impair respiratory system compliance. Hyperoxia-induced changes in lung parenchymal and small airway morphology were not further altered by intra-amniotic LPS. However, combined exposure to intra-amniotic LPS and hyperoxia increased the proportion of degranulating mast cells in the hilar airways.
Conclusion:
Intra-amniotic LPS amplified postnatal hyperoxia-induced AHR. This was associated with increased airway mast cell degranulation, which has previously been linked with hyperoxia-induced AHR. There were no morphologic changes of parenchyma or airways that would account for the LPS augmentation of hyperoxia-induced AHR.