Essential protective role of neuroactive steroids in the fetal and neonatal brain.

点击翻译按钮获取中文摘要

Brain injury may occur during complicated pregnancies and at birth, as well as in neonates following preterm labour, and is a major problem in neonatal medicine. The consequent nerve cell death leads to ongoing neurological impairment which represents a major cost to the individual and to the community. Neuroactive steroids are hormones related to the steroid hormone progesterone that have been shown to have a major influence on nerve cell activity and nervous transmission. While these hormones influence mood and behaviour in adult subjects, they have an even more important role in the fetus which is exposed to high levels of steroids from the placenta. The fetus is very sensitive to these neuroactive steroids and we have shown that they suppress the activity of the fetal brain so as to maintain the fetus in a sleep-like state during pregnancy. Periods of low oxygen supply (hypoxia) to the fetus may occur during pregnancy, as well as result from asphyxia at birth, and may lead to excessive excitation of nerve cells resulting in nerve cell death. Steroid-induced suppression reduces excitation of nerve cells and results in the fetus being resistant to excessive excitation. In this proposal we investigate the hypothesis that cells in the fetal brain modify the neuroactive steroid environment within the brain so as to suppress fetal brain activity further during times of hypoxic stress and, therefore, further protect the brain from damage caused by excessive excitation. These mechanisms may prevent brain injury due to placental insufficiency during pregnancy, asphyxia during birth and in premature babies. We will investigate whether the supplementation of these processes by administering neuroactive steroids may provide additional nerve protection during high-risk periods during pregnancy. These studies may identify a new as yet unexploited group of natural compounds which may improve infant health without adverse actions on the mother or baby.