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Updated: Sep 20, 2026

A Minimally Invasive Method for Intratracheal Instillation of Drugs in Neonatal Rodents to Treat Lung Disease
Published on: August 4, 2021
Ultrastructural changes in the lungs of neonatal rats intratracheally inoculated with meconium
J Martinez-Burnes1, A Lopez, 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 has been for many years an important cause of neonatal respiratory distress in newborn babies and sporadically reported in animals. This investigation was designed to study the ultrastructural and morphometric changes in the lungs of neonatal rats following the intratracheal inoculation of meconium. Seven-day-old Fischer-344 rats (n = 24) were randomly allocated in two groups. One group was intratracheally inoculated with saline solution and the second group received homologous meconium. Neonates were euthanatized at 1, 3 and 7 postinoculation days (PID) and lungs were examined by light and electron microscopy. Saline solution did not induce any ultrastructural changes in the lung. In contrast, meconium induced deciliation, recruitment of neutrophils and pulmonary alveolar macrophages to the bronchoalveolar space, intravascular sequestration of neutrophils and aggregation of platelets at PID 1 and 3. Other ultrastructural changes at PID 1 and 3 included interstitial edema and escape of red cells and fibrin into the alveolar space and interstitium. Interstitial edema and sequestration of neutrophils were responsible for the significant increase in thickness of alveolar septa. At PID 7 there was hyperplasia and enlargement of type II pneumocytes as well as interstitial proliferation of mesenchymal cells with intra-alveolar fibrosis. It was concluded that intratracheal inoculation of meconium in neonatal rats induces acute ultrastructural changes followed by a reparative response.
Insights
Meconium aspiration in neonatal rats causes lung injury, including cell damage and inflammation. A reparative response with cell growth and fibrosis occurs later.
Area of Science:
- Neonatal Pathology
- Pulmonary Medicine
- Ultrastructural Biology
Background:
- Meconium aspiration syndrome is a significant cause of respiratory distress in newborns.
- Understanding the lung's response to meconium is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the ultrastructural and morphometric changes in neonatal rat lungs after meconium aspiration.
- To characterize the acute and reparative phases of lung injury induced by meconium.
Main Methods:
- Intratracheal inoculation of meconium or saline in 7-day-old Fischer-344 rats.
- Light and electron microscopy examination of lung tissue at 1, 3, and 7 days post-inoculation.
- Morphometric analysis of alveolar septal thickness.
Main Results:
- Meconium induced lung injury, including deciliation, neutrophil recruitment, and macrophage activation.
- Ultrastructural changes observed included interstitial edema, red cell and fibrin extravasation, and platelet aggregation.
- By day 7, lung tissue showed type II pneumocyte hyperplasia, mesenchymal cell proliferation, and intra-alveolar fibrosis.
Conclusions:
- Intratracheal meconium instillation in neonatal rats triggers acute lung injury.
- The study reveals a subsequent reparative process involving cellular hyperplasia and fibrosis.

