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The effects of perinatal steroid therapy on growth factor levels during different stages of the developing brain
Burçin İşcan1, Funda Tuzun1, Serap Cilaker Micili2
1a Division of Neonatology, Department of Pediatrics , School of Medicine, Dokuz Eylul University , Izmir , Turkey.
Insights
Glucocorticoid (GC) exposure timing impacts fetal brain development. Early GC exposure significantly reduced neuronal count, while later exposure showed no difference, highlighting developmental stage sensitivity.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Excessive glucocorticoid (GC) exposure during fetal development can adversely affect the central nervous system (CNS).
- The timing of GC exposure may be critical in determining its impact on brain maturation.
- Understanding these effects is crucial for managing pregnancies involving GC therapy.
Purpose of the Study:
- To investigate the differential effects of betamethasone (a synthetic GC) on growth factor levels during various stages of brain maturation in a rat model.
- To evaluate how the timing of GC exposure influences neuronal development and growth factor responses.
Main Methods:
- Forty-two rat pups were divided into six groups based on the timing of betamethasone administration (postnatal days 1, 2, or 3).
- Control groups received saline injections.
- Neuronal density and growth factor levels were assessed via immunohistochemistry 24 hours after the final injection.
Main Results:
- Betamethasone administration on postnatal days 1 and 2 (equivalent to 22-28 human gestational weeks) significantly decreased hippocampal neuronal count compared to controls.
- Administration on postnatal day 3 (equivalent to 28-32 human gestational weeks) did not result in a significant difference in neuronal count.
- Growth factor responses varied depending on the timing of steroid exposure and the specific brain region examined.
Conclusions:
- The impact of glucocorticoids on neuronal count and growth factor response is critically dependent on the developmental stage of the brain at the time of exposure.
- This developmental timing sensitivity may explain the variable beneficial and deleterious effects of GCs on the developing central nervous system.
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.
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