The effects of perinatal steroid therapy on growth factor levels during different stages of the developing brain

J Matern Fetal Neonatal Med. 2017 Aug;30(15):1820-1828. doi: 10.1080/14767058.2016.1228051. Epub 2017 Feb 6.

Abstract

Objective: Excess glucocorticoid (GC) exposure on the fetal brain during critical stages of development has considerable effects on the development of the central nervous system (CNS). This study thus aimed to evaluate the differential effects of GC exposure on critical growth factor levels during different stages of brain maturation.

Methods: For this purpose, forty-two rat pups were divided into six groups based on the timing of betamethasone administration. Rats in the treatment groups were exposed to intraperitoneal betamethasone injections beginning at different time points (postnatal days 1, 2, and 3). Rats in the placebo group received the same volume of 0.9% saline via the same fashion. Pups were sacrificed at 24 h following the final injection for determining the neuronal density and immunohistochemical evaluation of critical growth factors.

Results: In the groups treated with betamethasone on postnatal day 1 (P1) and P2, which correspond to 22-24 and 24-28 gestational weeks in humans, the neuronal count in the hippocampal regions was significantly lower than their control groups. However, if steroid therapy was administered on P3, corresponding to 28-32 weeks in humans, no difference was observed between the two groups. Growth factors were affected in different ways depending on the steroid administration time and evaluated region.

Conclusions: The results suggest that the modulating effect of steroids on neuron count and growth factor response depends on the stage of brain development at the time of exposure. Therefore, this may be one of the key determinants affecting the deleterious and beneficial effects of GCs on the CNS.

Keywords: Perinatal steroid; betamethasone; brain development; growth factors; hippocampus; newborn rat.

MeSH terms

  • Animals
  • Animals, Newborn / growth & development
  • Animals, Newborn / physiology*
  • Betamethasone / administration & dosage*
  • Brain / drug effects*
  • Brain / growth & development*
  • Brain-Derived Neurotrophic Factor / analysis
  • Cell Count
  • Fibroblast Growth Factor 1 / analysis
  • Glucocorticoids / administration & dosage*
  • Hippocampus / chemistry
  • Hippocampus / cytology
  • Immunohistochemistry
  • Injections, Intraperitoneal
  • Intercellular Signaling Peptides and Proteins / analysis*
  • Neurons / cytology
  • Neurons / drug effects
  • Prefrontal Cortex / chemistry
  • Rats
  • Rats, Wistar
  • Receptor, Platelet-Derived Growth Factor alpha / analysis
  • Time Factors
  • Transforming Growth Factor alpha / analysis
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Brain-Derived Neurotrophic Factor
  • Glucocorticoids
  • Intercellular Signaling Peptides and Proteins
  • Transforming Growth Factor alpha
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 1
  • Betamethasone
  • Receptor, Platelet-Derived Growth Factor alpha