Defective pulmonary innervation and autonomic imbalance in congenital diaphragmatic hernia

摘要: Congenital diaphragmatic hernia (CDH) is associated with significant mortality due to lung hypoplasia and pulmonary hypertension. The role of embryonic innervation in normal development maldevelopment CDH has not been defined. We hypothesize that developmental defects intrapulmonary innervation, particular autonomic occur CDH. This abnormal may contribute postnatal physiological derangement To define patterns CDH, human control autopsy specimens were stained the pan-neural marker S-100. further characterize overall during murine nitrofen model was utilized. Immunostaining for protein gene product 9.5 (a pan-neuronal marker), tyrosine hydroxylase sympathetic vesicular acetylcholine transporter parasympathetic or VIP marker) performed on whole mounts analyzed via confocal microscopy three-dimensional reconstruction. Peribronchial perivascular neuronal staining pattern less complex than lung. In mice, reveals branching decreased neural tissue nitrofen-treated lungs from day 12.5 16.5 compared controls. Furthermore, exhibited altered a relative increase nerve decrease These results suggest primary defect resulting imbalance. Defective