Neurotrophins expression is decreased in lungs of human infants with congenital diaphragmatic hernia

Abstract

Neurotrophins expression is decreased in lungs of human infants with congenital diaphragmatic hernia Lynn D O'Hanlon, Sherry M Mabry, Ikechukwu I EkekezieChildren's Mercy Hospitals/University of Missouri-Kansas City School of Medicine, Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Kansas City, MO, USAObjectives: To evaluate neurotrophin (NT) (nerve growth factor [NGF], NT-3, and brain-derived neurotrophic factor [BDNF]) expression in autopsy lung tissues of human congenital diaphragmatic hernia (CDH) infants versus that of infants that expired with: 1) "normal" lungs (controls); 2) chronic lung disease (CLD); and 3) pulmonary hypertension (PPHN).Hypothesis: NT expression will be significantly altered in CDH lung tissue compared with normal lung tissue and other neonatal lung diseases.Study design: Immunohistochemical studies for NT proteins NGF, BDNF, and NT-3 were applied to human autopsy neonatal lung tissue samples.Subject selection: The samples included a control group of 18 samples ranging from 23-week gestational age to term, a CDH group of 15 samples, a PPHN group of six samples, and a CLD group of 12 samples.Methodology: The tissue samples were studied, and four representative slide fields of alveoli/saccules and four of bronchioles were recorded from each sample. These slide fields were then graded (from 0 to 3) by three blinded observers for intensity of staining.Results: BDNF, NGF, and NT-3 immunostaining intensity scores were significantly decreased in the CDH lung tissue (n=15) compared with normal neonatal lung tissue (n=18) (P<0.001). The other neonatal pulmonary diseases that were studied, CLD and PPHN, were much less likely to be affected and were much more variable in their neurotrophin expression.Conclusion: NT expression is decreased in CDH lungs. The decreased expression of NT in CDH lung tissue may suggest they contribute to the abnormality in this condition.Keywords: nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, neurotrophin-3, NT-3, chronic lung disease, persistent pulmonary hypertension, lung development