The effect of intrauterine inflammation on fetal cerebral hemodynamics and white matter injury in the chronically instrumented fetal sheep

我们建立了胎儿脑白质损伤（WMl）与干炎症相关的动物模型，以阐明其发病机制和预防措施。静脉输注粒细胞集落刺激因子和羊膜内毒素引起的宫内炎症导致胎儿缺氧，进而引起胎儿脑血流量代偿性增加，即脑跨效应（BSE）。随后，在内毒素输注24小时后，贫血性缺氧作为血流动力学损伤诱导BSE突然停止并导致局灶性WMI。本实验采用该模型，将胎羊分为4组。补氧组（n=3）在母体补氧已消除疯牛病后进行血流动力学损伤。在抗炎症组（n=2）中，在血流动力学损伤前，胎儿在诱导BSE的同时给予地塞米松。在泛炎症组（n=2）中，在初始贫血性损伤诱导的BSE后再次进行贫血性缺氧，而不进行炎症准备。对照组未进行炎症性和缺氧性损伤（n 3）。因此，补氧组3例胎儿中有2例出现心室周围局灶性和/或皮质下多灶性WMI，抗炎组1例，非炎症组2例，对照组无一例。基于这些结果，我们认为(1)BSE的突然停止，即使是由炎症或缺氧引起的，也可能是胎儿脑WMI发生的必要条件；(2)补充氧气和地塞米松可能无法阻止BSE相关WMI的发生。

We developed an animal model of fetal cerebral white matter injury (WMl) associated with inflammation in stem to clarify the pathogenesis of and preventive measures against it using chronically instrumented fetal sheep; intrauterine inflammation, induced by the infusion with intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin, led fetal hypoxia and then resulted in a compensatory increase of fetal cerebral blood flow, i. e., brain span effect (BSE). Subsequently, at 24 hours after the endotoxin infusion, anemic hypoxia as a hemodynamic insult induced sudden cessation of BSE and resulted in focal WMI. In the current experiment using this model, fetal sheep were divided into 4 groups. In an oxygen supplement group (n=3), the hemodynamic insult was performed after the BSE bad been already cancelled by maternal oxygen supplement. In an anti-inflammation group (n=2), fetuses were administered dexamethasone simultaneously with the BSE induction before the hemodynamic insult. In a pan-inflammation group (n=2), anemic hypoxia was done again after the initial anemic insult induced the BSE without the inflammatory preparation. Neither inflammatory nor hypoxic insult was done in a control group (n 3). Consequently, periventricular focal and/or subcortical multi-focal WMI was found in 2 of the 3 fetuses in the oxygen supplement group, 1 of the 2 in the anti-inflammation group and 2 of the 2 in the non-inflammation group but none in the control group. Based on these results, it was considered that (1) sudden cessation of BSE, even if induced by inflammation, or hypoxia, might be essential in the genesis of fetal cerebral WMI and (2) both oxygen supplement and dexamethasone might be unable to prevent the development of the WMI associated with BSE.