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-nitro-phenylether (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.

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Keywords Congenital diaphragmatic hernia, calcitonin gene-related peptide, pulmonary hypertension, pulmonary neuroendocrine cells
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Journal Journal of Pediatric Surgery
IJsselstijn, H, Perrin, D.G, de Jongste, J.C, Cutz, E, & Tibboel, D. (1995). Pulmonary neuroendocrine cells in neonatal rats with congenital diaphragmatic hernia. Journal of Pediatric Surgery, 30(3), 413–415. doi:10.1016/0022-3468(95)90044-6