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

脑损伤可能发生在复杂的怀孕期间和出生时，以及早产后的新生儿中，并且是新生儿医学中的主要问题。随之而来的神经细胞死亡导致持续的神经损伤，这对个人和社区来说是一个重大的代价。神经活性类固醇是与类固醇激素孕酮相关的激素，其已被证明对神经细胞活性和神经传递具有重大影响。虽然这些激素影响成年受试者的情绪和行为，但它们在胎儿中具有更重要的作用，胎儿暴露于胎盘中的高水平类固醇。胎儿对这些神经活性类固醇非常敏感，我们已经证明它们抑制胎儿大脑的活动，从而使胎儿在怀孕期间保持睡眠状态。胎儿低氧供应（缺氧）的时期可能发生在怀孕期间，以及出生时窒息的结果，并可能导致神经细胞过度兴奋，导致神经细胞死亡。类固醇引起的抑制降低了神经细胞的兴奋，导致胎儿对过度兴奋产生抵抗力。在这个建议中，我们调查的假设，胎儿大脑中的细胞修改大脑内的神经活性类固醇环境，以抑制胎儿大脑活动进一步在缺氧应激的时候，因此，进一步保护大脑免受过度兴奋造成的损害。这些机制可以防止由于怀孕期间胎盘功能不全，出生时窒息和早产儿造成的脑损伤。我们将研究是否通过给予神经活性类固醇补充这些过程可能会提供额外的神经保护在怀孕期间的高风险时期。这些研究可能会发现一组新的尚未开发的天然化合物，这些化合物可能会改善婴儿健康，而不会对母亲或婴儿产生不利影响。

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.