The Role of Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor in Chronic Fetal Oxygen Deprivation

Abstract

The aim of the study was to define the role of brain-derived and glial cell line-derived neurotrophic factors (BDNF and GDNF) in realization of compensative and adaptive mechanisms of a neonatal organism to hypoxia. Materials and Methods. The experiments in vivo have been carried out on pregnant C57BL/6 mice (n=36). Chronic hypobaric hypoxia has been modeled in different pregnancy trimesters. On gestation days E19-20, concentration of BDNF and GDNF in the blood of the pregnant females was determined by enzyme immunoassay. Further, the number of neonatal mice, their weight and body length parameters have been assessed. Parturient mothers (n=88) and their newborn babies followed up at the Clinic of Obstetrics and Gynecology of Pavlov University took part in the clinical investigations. Concentration of BDNF, GDNF, neuron-specific enolase (NSE), and hypoxia-inducible factor (HIF-1β) in the fetal cord blood has been determined by ELISA. The obtained data were retrospectively compared with cardiotocography, dopplerometry, presence of meconium-stained amniotic fluid and the neonate state at birth, assessment according to the Apgar score, and the course of adaptation period. Results. Chronic hypobaric hypoxia in pregnant mice in trimester I and II resulted in the significant decrease of BDNF and GDNF level, decrease in the number of embryos, and in significant changes in weight/height characteristics of the newborn pups. According to the clinical observations, an increased expression of the neurotrophic factors BDNF, GDNF provides protection to a neonate even if hypoxia factors are present and realized. A low content of BDNF and GDNF was observed in the group of infants with a high risk of developing unfavorable hypoxic damaging effects.

Clinical Importance of Serum BDNF (Brain-Derived Neurotrophic Factor) Level for the Management of Pregnancies Complicated With Meconium-Stained Amniotic Fluid

“…BDNF recently became a prominent mediator to determine the relationship between neuronal damage after intrauterine adverse events such as fetal hypoxia [ 14 ]. The critical role in the protection of neuronal survival causes significant alteration of the level of BDNF [ 16 ].…”

“…The pleiotropic effects of neurotrophins such as BDNF were also studied for the effects on airway structure, function, and lung diseases [ 13 ]. Recent studies suggest that BDNF might also be a novel marker to predict neonatal hypoxic events during labor [ 14 ]. In previous studies, it has been shown that BDNF could pass through the blood-brain barrier, and levels of BDNF are similar in cord blood and fetal brain [ 15 ].…”

“…In previous studies, it has been shown that BDNF could pass through the blood-brain barrier, and levels of BDNF are similar in cord blood and fetal brain [ 15 ]. Shchelchkova et al also defined the protective role of BDNF in the case of fetal hypoxia [ 14 ].…”