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A Minimally Invasive Method for Intratracheal Instillation of Drugs in Neonatal Rodents to Treat Lung Disease
Published on: August 4, 2021
Microscopic changes induced by the intratracheal inoculation of amniotic fluid and meconium in the lung of neonatal
J Martínez-Burnes1, A López, G M Wright
1Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Canada. jmburnes@uat.edu.mx
Abstract:
Meconium aspiration syndrome is a major contributor to neonatal respiratory distress in infants and it has been sporadically recognized in neonatal animals. This investigation was designed to study the short and long term effects of meconium and amniotic fluid in the lungs of neonatal rats. Seven-day-old rats (n = 123) divided in three groups were intratracheally inoculated with saline solution, amniotic fluid or meconium. Rats were euthanatized on 1, 3, 7, 14, 28, 56 and 112 postinoculation days (PID) and the lungs were examined by light microscopy. Saline solution did not induce any change while amniotic fluid elicited only a mild foreign body response which disappeared by PID 14. In contrast, meconium induced an exudative alveolitis characterized by recruitment of neutrophilsn in the bronchoalveolar spaces. Meconium also induced atelectasis, hyperinflation and thickening of alveolar septa all of which had disappeared by PID 14. Starting at PID 7, neutrophils were progressively replaced by macrophages, giant cells, and some fibroblasts. There were sporadic foci of mineralization starting at PID 14 and lasting up to PID 112. Some mineralized foci became lined with cuboidal epithelial cells at PID 28. Meconium was slowly degraded but still evident by PID 112. It was concluded that inoculation of meconium in neonatal rats induces acute microscopic changes typical of meconium aspiration syndrome. The long term lesions induced by meconium consisted of persistent multifocal histiocytic alveolitis and bronchiolitis reaction with occasional foci of calcification.
Insights
Meconium aspiration syndrome in neonatal rats causes acute lung injury and persistent inflammation, including calcification. These findings model human infant respiratory distress from meconium exposure.
Area of Science:
- Veterinary Pathology
- Neonatal Physiology
- Respiratory Medicine
Background:
- Meconium aspiration syndrome (MAS) is a significant cause of neonatal respiratory distress in human infants.
- MAS has been observed in neonatal animals, but its pathological effects require detailed study.
- Understanding MAS pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the short- and long-term pulmonary effects of meconium and amniotic fluid exposure in neonatal rats.
- To characterize the histological changes associated with meconium aspiration.
- To establish a preclinical model for studying MAS.
Main Methods:
- Neonatal rats (n=123) were divided into three groups: saline, amniotic fluid, and meconium.
- Intratracheal inoculation was performed in 7-day-old rats.
- Lungs were examined via light microscopy at multiple time points post-inoculation (1-112 days).
Main Results:
- Saline caused no changes; amniotic fluid induced a mild, transient foreign body response.
- Meconium induced acute exudative alveolitis with neutrophil recruitment, atelectasis, and alveolar septal thickening.
- Long-term effects included persistent histiocytic alveolitis, bronchiolitis, and multifocal calcification, with meconium evident up to 112 days.
Conclusions:
- Intratracheal meconium instillation in neonatal rats accurately replicates the acute microscopic pathology of MAS.
- The study demonstrates persistent inflammatory and calcific lung lesions following meconium exposure.
- This rat model is suitable for investigating the pathophysiology and potential therapies for MAS.

