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Pulmonary neuroendocrine cells in neonatal rats with congenital diaphragmatic hernia
H IJsselstijn1, D G Perrin, J C de Jongste
1Department of Pediatric Surgery, Erasmus University, Rotterdam, The Netherlands.
Insights
Congenital diaphragmatic hernia (CDH) in neonatal rats shows an increased number of pulmonary neuroendocrine cell clusters (NEB). This finding may impact lung development and vascular tone regulation in CDH infants.
Area of Science:
- Pulmonary Medicine
- Developmental Biology
- Neonatal Research
Background:
- Congenital diaphragmatic hernia (CDH) leads to significant infant mortality due to lung hypoplasia and persistent pulmonary hypertension.
- Pulmonary neuroendocrine cells (PNEC) and their product, calcitonin gene-related peptide (CGRP), are crucial for lung development and pulmonary vascular tone regulation.
- Elevated CGRP levels are observed during chronic hypoxia, suggesting a role in vascular adaptation.
Purpose of the Study:
- To investigate the morphometric changes of CGRP-immunoreactive PNEC clusters (neuroepithelial bodies, NEB) in a rat model of CDH.
- To determine if NEB number and size are altered in neonatal rats with experimentally induced CDH.
Main Methods:
- CDH was induced in Sprague Dawley rats using Nitrofen exposure during gestation.
- Lung tissues from neonatal rats with and without CDH were immunostained for CGRP, a marker for NEB.
- A semiautomatic image analysis system was used to quantify NEB number per lung area and NEB size.
Main Results:
- Neonatal rats with CDH exhibited a significantly higher number of NEB per unit lung surface area compared to controls.
- While NEB size was larger in the CDH group, this difference was not statistically significant.
- This study provides the first evidence of altered NEB morphology in a CDH model.
Conclusions:
- The increased NEB number in CDH lungs suggests a potential compensatory mechanism or developmental alteration.
- Further research is needed to understand the functional implications of these NEB changes on vasoactive mediator balance in CDH.
- Investigating these findings in human CDH cases is crucial for clinical relevance.
Abstract:
Lung hypoplasia and persistent pulmonary hypertension are the principal causes of high mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Amine- and peptide-producing pulmonary neuroendocrine cells (PNEC), widely distributed throughout the airway mucosa, are thought to play an important role in both pulmonary development and regulation of pulmonary vascular tone. Furthermore, recent studies show increased levels of calcitonin gene-related peptide (CGRP), a pulmonary vasodilator produced by PNEC, during chronic hypoxia. The article reports data on morphometric analysis of CGRP immunoreactive PNEC clusters (neuroepithelial bodies, NEB) in a rat model of CDH. CDH was induced in neonatal Sprague Dawley rats by oral administration of 2,4-dichloro-phenyl-p-nitrophenylether (Nitrofen; Rohm Haas, Philadelphia, PA) to the mother at 10 days of gestation. Sections of lungs from term neonatal rats with and without CDH and controls were immunostained for CGRP (marker of NEB) with specific antibody against rat CGRP. NEB size and number of NEB/area of lung were assessed using a semiautomatic image analysis system. In lungs of neonatal rats with CDH, the number of NEB per surface area of lung parenchyma was significantly increased compared with the age-matched controls. Although the mean size of NEB was larger in CDH, the differences were not significant. This is the first study of PNEC in CDH. Whether the phenomenon observed in this study results in altered NEB function including imbalance in vasoactive mediators requires further studies, especially in the human being.