PROTECTING THE PRETERM FETAL BRAIN FROM HYPOXIA AND INFECTION: A HEALTHY START TO LIFE.

胎儿时期的脑损伤是日后神经系统问题（如脑瘫）的重要原因。最近的研究表明，在婴儿中检测到的脑损伤通常是由分娩前子宫内的不利条件引起的，但确切原因尚不清楚。同样明显的是，早产婴儿遭受严重脑损伤的风险增加。近年来，很明显，母亲感染可能与早产和脑损伤有关。有人提出，在感染过程中释放的某些化学物质（细胞因子）可以穿过胎盘到达胎儿，引起炎症变化，从而导致脑损伤。我们已经证明，一种诱导炎症的化学物质（细菌内毒素）给予未成熟的胎羊，会导致与脑瘫相似的脑损伤。这为测试已知阻断细胞因子和其他炎症标志物作用的药物提供了一个极好的模型；目前还没有有效的策略来治疗或预防缺氧和炎症性脑损伤，部分原因是我们对损伤发生的方式和时间一无所知。我们将测试两种化学品的效果；n -乙酰半胱氨酸，已知可阻断炎性细胞因子的产生，以及自然产生的糖蛋白促红细胞生成素，可防止神经元死亡（细胞凋亡）。我们希望通过阻断这些通路，我们可以防止未成熟的胎儿在妊娠期间暴露于感染时发生脑损伤。我们期望这个项目将提供重要的新信息，帮助我们了解母亲感染如何导致胎儿脑损伤，并为预防或治疗脑损伤的策略提供新的途径。

Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. In recent years it has become evident that infections in the mother may be linked to both premature birth and brain damage. It has been proposed that certain chemicals (cytokines), which are released during an infection, can cross the placenta to the fetus causing inflammatory changes that lead to brain damage. We have shown that an inflammatory inducing chemical (bacterial endotoxin) administered to immature fetal sheep induces brain damage similar to that seen in cerebral palsy. This provides an excellent model for testing agents that are known to block the action of cytokines and other markers of inflammation; currently there is no effective strategy for the treatment or prevention of hypoxia and inflammatory induced injury of the brain partly due to our ignorance about how and when the damage is occurring. We will test the effects of two chemicals; N-acetyl cysteine, which is known to block the generation of inflammatory cytokines, and the naturally occurring glycoprotein erythropoietin, which prevents death of neurons (apoptosis). We hope that by blocking these pathways we may be able to prevent brain injury from occurring when the immature fetus is exposed to an infection during gestation. We expect that this project will provide important novel information that helps us to understand how infection in the mother can cause brain injury in the fetus and provide a new approach for strategies to prevent or treat brain injury.