Bronchopulmonary innervation defects in infants and rats with congenital diaphragmatic hernia.
BACKGROUND
Pulmonary morbidity in survivors of congenital diaphragmatic hernia (CDH) is caused by hypoplasia, barotraumas, or other reasons. We have previously shown deficient tracheal innervation in rats with CDH. Now we examine whether bronchopulmonary innervation is also abnormal in both infants and rats with CDH.


METHODS
Sections of E15, E18, and E21 rat lungs were immunostained for Protein gene product 9.5 and S100 antibodies. Similar immunostaining was performed on tissue from infants dying from CDH (n = 6) and other causes (n = 6) with Neurofilament, S100, and Rearranged during transfection antibodies. Nerve trunks/bronchus were counted, and the proportion of glial and RET-positive cells/bronchial surface was calculated. Glial cell-line derived neurotrophic factor protein and mRNA were measured in rat lungs.


RESULTS
Nerve trunks/bronchus were decreased in infants and rat fetuses with CDH. In contrast, glial and RET-positive cells/bronchial surface were increased in infants and rats with CDH. Both lungs were equally affected. GDNF protein was high, whereas GDNF mRNA was decreased in preterm animals with CDH.


CONCLUSIONS
The lungs of infants and rats with CDH have decreased neural components compensated by increased supporting glial cells and persistence high expression of RET and GDNF protein. Because bronchopulmonary innervation controls airway smooth muscle, vessels, and glandular secretions, it is tempting to hypothesize that these deficiencies might play a role in respiratory morbidity in CDH.
Department of Pediatric Surgery and Research Laboratory, Hospital Universitario La Paz, 28046 Madrid, Spain.
Federica
F
Pederiva
Rosa Aras
RA
Lopez
Jose I
JI
Rodriguez
Leopoldo
L
Martinez
Juan A
JA
Tovar
D000818:Animals; D001980:Bronchi / Q000002:abnormalities / Q000294:innervation; D004195:Disease Models, Animal; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006548:Hernia, Diaphragmatic / Q000196:embryology / Q000473:pathology*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008168:Lung / Q000002:abnormalities* / Q000294:innervation* / Q000473:pathology; D009432:Neural Crest / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D010647:Phenyl Ethers; D011247:Pregnancy; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000002:abnormalities / Q000294:innervation; D043222:Ubiquitin Thiolesterase / Q000276:immunology / Q000378:metabolism
D051100:Glial Cell Line-Derived Neurotrophic Factor; D010647:Phenyl Ethers; C482860:UCHL1 protein, human; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; C007350:nitrofen