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

宫内炎症对长期仪器胎羊胎儿脑血流动力学及脑白质损伤的影响

• 批准号: 18591213
• 负责人: MATSUDA Tadashi
• 金额: $ 2.57万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591213/
• 关键词: intrauterine inflammation; cerebral blood flow; brain sparing effect; cerebral ischemia; cerebral white matter damage; periventricular leukomalacia; fetus; sheep; 実験動物モデル; 脳室周囲白質軟化; 近赤外線分光法; 壊死性臍帯炎; エンドトキシン; 顆粒球コロニー刺激因子

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.

为探讨慢性宫内感染致胎羊脑白色损伤（WM 1）的发病机制及预防措施，我们采用慢性宫内感染法建立了WM 1伴脑干炎症的动物模型。例如，脑广度效应（brain span effect，BSE）随后，在内毒素输注后24小时，作为血流动力学损伤的贫血性缺氧诱导BSE突然停止并导致局灶性出血。在本实验中，使用该模型，将胎羊分为4组。给氧组（n=3）在BSE消失后再行血流动力学检查。在抗炎组（n=2）中，胎儿在血流动力学损伤前在BSE诱导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BSE后再次进行贫血性缺氧，而不使用炎症制剂。对照组（n 3）既不进行炎症性损伤，也不进行缺氧性损伤。因此，在补氧组的3只胎儿中的2只、抗炎组的2只和非炎症组的2只中发现了脑室周围局灶性和/或皮质下多灶性水肿，而在对照组中没有发现。基于这些结果，认为（1）BSE的突然停止，即使是由炎症或缺氧引起的，也可能是胎儿脑水肿发生的关键;（2）供氧和地塞米松可能无法阻止与BSE相关的脑水肿的发展。

项目成果

induction of necrotizing fuhisitis by fetal administration of intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin in premature fetal sheep

胎儿静脉注射粒细胞集落刺激因子和羊膜腔内毒素诱导早产胎羊坏死性Fuhisitis

• 发表时间: 2007
• 期刊: Pediatr Res 62
• 作者: Watanabe T;Matsuda T;Hanita T;Okuyama K;Cho K;Kobayashi K;Kobayashi Y.
• 通讯作者: Kobayashi Y.

Induction of necrotizing funisitis by fetal administration of intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin in premature fetal sheep

• DOI: 10.1203/pdr.0b013e31815991bf
• 发表时间: 2007-12-01
• 期刊: PEDIATRIC RESEARCH
• 影响因子: 3.6
• 作者: Watanabe, Tatsuya;Matsuda, Tadashi;Kobayashi, Yoshiyasu
• 通讯作者: Kobayashi, Yoshiyasu

Funisitis

绳索炎

• 发表时间: 2007
• 期刊: Medical View, Co, . Ltd., Preterm Labor
• 作者: Watanabe T;Matsuda T;Hanita T;Okuyama K;Cho K;Kobayashi K;Kobayashi Y.;Tadashi Matsuda
• 通讯作者: Tadashi Matsuda

ヒツジ胎仔を用いた子宮内炎症がびまん性脳白質傷害に与える影響の解析

羊胎宫内炎症对弥漫性脑白质损伤的影响分析

• 发表时间: 2008
• 作者: 北西龍太;松田 直
• 通讯作者: 松田 直

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

宫内炎症对长期仪器胎羊胎儿脑血流动力学及脑白质损伤的影响

• 发表时间: 2008
• 作者: Kitanishi Ryuta;Tadashi matsuda
• 通讯作者: Tadashi matsuda