Document Detail

Defective pulmonary innervation and autonomic imbalance in congenital diaphragmatic hernia.
MedLine Citation:
PMID:  22114150     Owner:  NLM     Status:  MEDLINE    
Congenital diaphragmatic hernia (CDH) is associated with significant mortality due to lung hypoplasia and pulmonary hypertension. The role of embryonic pulmonary innervation in normal lung development and lung maldevelopment in CDH has not been defined. We hypothesize that developmental defects of intrapulmonary innervation, in particular autonomic innervation, occur in CDH. This abnormal embryonic pulmonary innervation may contribute to lung developmental defects and postnatal physiological derangement in CDH. To define patterns of pulmonary innervation in CDH, human CDH and control lung autopsy specimens were stained with the pan-neural marker S-100. To further characterize patterns of overall and autonomic pulmonary innervation during lung development in CDH, the murine nitrofen model of CDH was utilized. Immunostaining for protein gene product 9.5 (a pan-neuronal marker), tyrosine hydroxylase (a sympathetic marker), vesicular acetylcholine transporter (a parasympathetic marker), or VIP (a parasympathetic marker) was performed on lung whole mounts and analyzed via confocal microscopy and three-dimensional reconstruction. Peribronchial and perivascular neuronal staining pattern is less complex in human CDH than control lung. In mice, protein gene product 9.5 staining reveals less complex neuronal branching and decreased neural tissue in nitrofen-treated lungs from embryonic day 12.5 to 16.5 compared with controls. Furthermore, nitrofen-treated embryonic lungs exhibited altered autonomic innervation, with a relative increase in sympathetic nerve staining and a decrease in parasympathetic nerve staining compared with controls. These results suggest a primary defect in pulmonary neural developmental in CDH, resulting in less complex neural innervation and autonomic imbalance. Defective embryonic pulmonary innervation may contribute to lung developmental defects and postnatal physiological derangement in CDH.
Nikesh R Lath; Csaba Galambos; Alejandro Best Rocha; Marcus Malek; George K Gittes; Douglas A Potoka
Publication Detail:
Type:  Journal Article     Date:  2011-11-23
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  302     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-13     Completed Date:  2012-03-27     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L390-8     Citation Subset:  IM    
Department of Surgery, University of Pittsburgh, PA, USA.
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MeSH Terms
Biological Markers / metabolism
Case-Control Studies
Hernia, Diaphragmatic / chemically induced,  congenital*,  pathology
Infant, Newborn
Lung / embryology,  innervation*,  pathology
Parasympathetic Nervous System / embryology,  metabolism,  pathology*
Phenyl Ethers
S100 Proteins / metabolism
Sympathetic Nervous System / embryology,  metabolism,  pathology*
Vasoactive Intestinal Peptide / metabolism
Vesicular Acetylcholine Transport Proteins / metabolism
Grant Support
Reg. No./Substance:
0/Biological Markers; 0/Phenyl Ethers; 0/S100 Proteins; 0/Slc18a3 protein, mouse; 0/Vesicular Acetylcholine Transport Proteins; 1836-75-5/nitrofen; 37221-79-7/Vasoactive Intestinal Peptide

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