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

Authors O’Hanlon L, Mabry S, Ekekezie I

Received 28 August 2013

Accepted for publication 22 October 2013

Published 3 February 2014 Volume 2014:4 Pages 9—15

DOI https://doi.org/10.2147/RRN.S53673

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4


Lynn D O'Hanlon, Sherry M Mabry, Ikechukwu I Ekekezie

Children's Mercy Hospitals/University of Missouri-Kansas City School of Medicine, Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Kansas City, MO, USA

Objectives: 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

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