BACKGROUND: Tracheobronchial motility influences lung development. Lung hypoplasia and lung sequelae accompany congenital diaphragmatic hernia (CDH) in which the vagus nerves and esophageal innervation are abnormal. As the vagus supplies tracheal innervation, this study tested the hypothesis that it might also be abnormal in rats with CDH. MATERIAL AND METHODS: Intrinsic ganglia were counted and measured in whole mount acetylcholinesterase-stained tracheas from CDH and control E21 fetal rats. The relative surfaces occupied by neural structures were measured in tracheal sections immunostained for p75(NTR) and PGP 9.5. PGP 9.5 protein and mRNA expression were determined. Mann-Whitney tests were used for comparisons between groups using P < .05 as significant. RESULTS: p75(NTR) staining showed the neural crest origin of tracheal innervation. Scarce neural structures and smaller ganglia were found in CDH fetuses. PGP 9.5 protein expression was decreased in CDH fetuses, whereas PGP 9.5 mRNA levels were increased in comparison with controls. CONCLUSIONS: Decreased density of neural structures and size of intramural ganglia, reduced expression of neural tissue and PGP 9.5 protein, and increased levels of PGP 9.5 mRNA reveal deficient tracheal innervation in rats with CDH. If similar anomalies exist in the human condition, they could contribute to explaining the pathogenesis of lung hypoplasia and bronchopulmonary sequelae.
BACKGROUND:Tracheobronchial motility influences lung development. Lung hypoplasia and lung sequelae accompany congenital diaphragmatic hernia (CDH) in which the vagus nerves and esophageal innervation are abnormal. As the vagus supplies tracheal innervation, this study tested the hypothesis that it might also be abnormal in rats with CDH. MATERIAL AND METHODS: Intrinsic ganglia were counted and measured in whole mount acetylcholinesterase-stained tracheas from CDH and control E21 fetal rats. The relative surfaces occupied by neural structures were measured in tracheal sections immunostained for p75(NTR) and PGP 9.5. PGP 9.5 protein and mRNA expression were determined. Mann-Whitney tests were used for comparisons between groups using P < .05 as significant. RESULTS:p75(NTR) staining showed the neural crest origin of tracheal innervation. Scarce neural structures and smaller ganglia were found in CDH fetuses. PGP 9.5 protein expression was decreased in CDH fetuses, whereas PGP 9.5 mRNA levels were increased in comparison with controls. CONCLUSIONS: Decreased density of neural structures and size of intramural ganglia, reduced expression of neural tissue and PGP 9.5 protein, and increased levels of PGP 9.5 mRNA reveal deficient tracheal innervation in rats with CDH. If similar anomalies exist in the human condition, they could contribute to explaining the pathogenesis of lung hypoplasia and bronchopulmonary sequelae.
Authors: Julie Rhodes; Deeksha Saxena; GuangFeng Zhang; George K Gittes; Douglas A Potoka Journal: Am J Physiol Lung Cell Mol Physiol Date: 2015-05-01 Impact factor: 5.464
Authors: Nikesh R Lath; Csaba Galambos; Alejandro Best Rocha; Marcus Malek; George K Gittes; Douglas A Potoka Journal: Am J Physiol Lung Cell Mol Physiol Date: 2011-11-23 Impact factor: 5.464
Authors: Leopoldo Martínez; Rosa Aras-López; Sara Lancha; María Teresa Vallejo-Cremades; Federica Pederiva; Liu XiaoMei; Juan Antonio Tovar Journal: Pediatr Surg Int Date: 2011-02 Impact factor: 1.827
Authors: Montserrat Bret; Ana Lourdes Luis; Emilio Cuesta; Federica Pederiva; Rosa Aras; Leopoldo Martinez; Juan A Tovar Journal: Pediatr Surg Int Date: 2010-01 Impact factor: 1.827