FETAL BRAIN INJURY RESULTING FROM INTRAUTERINE INFECTION: LONG TERM CONSEQUENCES AND THE POTENTIAL FOR INTERVENTION

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。不幸的是，目前还不可能预防或有效治疗胎儿或新生儿的脑损伤，部分原因是对损伤发生的方式和时间的无知。近年来，很明显，母亲的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，导致脑损伤。然而，尽管在对女性的研究中显示出了这种关联，但几乎没有证据表明感染确实会对胎儿造成脑损伤。该项目将确定炎症诱导化学物质（细菌内毒素）对胎儿大脑的影响，以及它在胎儿体内建立的炎症模式。我们还将研究由内毒素引起的新生羔羊脑损伤的影响，并将其与行为的改变联系起来。一旦我们确定了内毒素对大脑结构的影响，我们将测试已知能阻断炎症细胞因子作用的化学物质的影响。我们希望，通过阻断导致有害细胞因子产生的化学途径，我们也许能够防止胎儿受到母体感染时发生脑损伤。预计该项目将提供重要信息，帮助我们了解母亲感染如何导致胎儿脑损伤。如果要制定预防或治疗脑损伤的策略，这些信息是至关重要的。

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. Unfortunately, at present, it is not possible to prevent or effectively treat brain damage in the fetus or newborn, partly due to ignorance about how and when the damage is occurring. 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 the certain chemicals (cytokines) which are released during an infection can across the placenta to the fetus, causing inflammatory changes that lead to brain damage. However, although associations have been shown in studies of women, there is little evidence that infections actually cause brain damage in the fetus. This project will define the effects of an inflammation inducing chemical (bacterial endotoxin) on the fetal brain and the pattern of inflammation it sets up in the fetus. We will also examine the effects of brain damage caused by endotoxin in the newborn lamb, and relate this to alterations in behaviour. Once we have defined the effects of endotoxin on brain structure, we will test the effects of chemicals that are known to block the actions of inflammatory cytokines. We hope that by blocking the chemical pathway that leads to the production of harmful cytokines we may be able to prevent brain injury from occurring when the fetus is exposed to an infection in the mother. It is expected that this project will provide important information that helps us to understand how infection in the mother can cause brain injury in the fetus. This information is vital if strategies to prevent or treat brain injury are to be developed.