22 Decreased Neurotrophin Expression in Congenital Diaphragmatic Hernia Human Lung Tissue.

Abstract

Top of pageAbstract Background: Neurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)] are growth factors that function as mediators for the development, survival and differentiation of neurons and other types of cells. During normal tissue morphogenesis, neurogenesis and myogenesis proceed as tightly linked processes. In the condition, congenital diaphragmatic hernia (CDH), there is failure of the diaphragm muscle to develop with consequent pulmonary hypoplasia and pulmonary hypertension. The probability that impaired neurogenesis, or coordination of neuro and myogenesis, underlies the disrupted development of the diaphragm muscle in CDH, needs to be explored. Objectives: To determine the expression of neurotrophic factors (NGF, NT-3 and BDNF) in neonatal lung disease; specifically congenital diaphragmatic hernia (CDH), persistent pulmonary hypertension (PPHN) and chronic lung disease (CLD) vs. normal lung tissue. Methods: Immunohistochemical studies for neurotrophin proteins (specific antibody staining using polyclonal rabbit anti-human NGF, BDNF and NT-3) were applied to human neonatal lung tissue samples. The samples included a control group of 18 samples ranging from 23wk EGA to term, a CDH group of 15 samples, a PPHN group of 6 samples and a CLD group of 12 samples. The tissue samples were studied and 4 representative slide fields of aveoli/saccules and 4 of bronchioles were recorded from each sample. These slide fields were then graded (from 0-3) by several blinded observers for intensity of staining. Results: BDNF, NGF and NT-3 immunostaining intensity scores were significantly less in the CDH lung tissue samples (n 15) compared to normal neonatal lung tissue (n 18) (p<0.001). Similarly, PPHN lung tissue (n 6) scored less than normal lung tissue, although not statistically significant; likely due to few samples studied. Chronic lung disease tissue (n 12) did not appear to differ in their neurotrophic staining intensity compared to normal neonatal lung tissue. Conclusion: Neurotrophin expression is decreased in CDH lungs. The decreased expression of neurotrophins in CDH lung tissue suggests they contribute to the abnormality in this condition. Further studies are needed to explore the role of deficient neurotrophin expression in the development of CDH.