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Development of a guinea pig model of chorioamnionitis and fetal brain injury.

机译:绒毛膜羊膜炎和胎儿脑损伤的豚鼠模型的开发。

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摘要

Objective. To develop a guinea pig model of chorioamnionitis in order to study the mechanism(s) leading to fetal brain injury.;Introduction. It is postulated that the risk of developing cerebral palsy is increased after exposure to chorioamnionitis in utero due to activation of proinflammatory cytokines. Using a guinea pig model, studies were performed in order to determine the effects of infection on amniotic fluid cytokine levels and fetal brain injury characteristic of cerebral palsy.;Methodology. Pregnant guinea pigs at approximately 70% gestation (45--50 days of 65 day gestation) were intracervically inoculated with Eschericia coli. Guinea pigs were euthanized two to fourteen days after bacterial inoculation. For each fetus, the amniotic fluid and brain were collected for further analysis. Maternal blood and amniotic fluid samples were analyzed for proinflammatory cytokine levels using cytokine-specific enzyme-linked immunosorbent assay kits. Slides of coronally-sliced fetal brains were stained for cell death using the NeuroTacs system, a TUNEL-like stain specialized for central nervous system tissue.;Results. Amniotic fluid proinflammatory cytokines were significantly higher in fetal samples obtained from mothers subjected to intracervical inoculation with bacteria as compared to controls. This was true regardless of whether microbiologic chorioamnionitis was confirmed, indicating that indirect exposure to infectious agents was sufficient to cause an elevated inflammatory response in the fetus. Levels of amniotic fluid proinflammatory cytokines decreased after a period of 4--5 days. Levels of white matter injury were greater in fetuses exposed to bacterial infection in utero as compared to controls.;Conclusions. Chorioamnionitis in guinea pigs results in increased maternal and fetal proinflammatory cytokines and fetal brain injury similar to that which occurs in cerebral palsy.
机译:目的。建立豚鼠绒毛膜羊膜炎模型,以研究导致胎儿脑损伤的机制。据推测,由于促炎性细胞因子的激活,子宫内暴露于绒毛膜羊膜炎后患脑瘫的风险增加。为了确定感染对羊水细胞因子水平和脑瘫特征性胎儿脑损伤的影响,使用了豚鼠模型进行了研究。大约70%妊娠(65天妊娠的45--50天)的怀孕豚鼠经大肠埃希氏菌接种。细菌接种后2到14天对豚鼠实施安乐死。对于每个胎儿,收集羊水和大脑以进行进一步分析。使用细胞因子特异性酶联免疫吸附测定试剂盒分析了母血和羊水样品的促炎细胞因子水平。使用NeuroTacs系统对冠状切片的胎儿大脑切片进行细胞死亡染色,这是专门用于中枢神经系统组织的TUNEL样染色。与对照相比,从接受细菌内接种的母亲获得的胎儿样品中,羊水促炎细胞因子明显更高。不管是否确认了微生物性绒毛膜羊膜炎,这都是事实,这表明间接接触感染因子足以引起胎儿炎症反应升高。 4--5天后,羊水促炎细胞因子水平降低。与对照组相比,子宫内受到细菌感染的胎儿的白质损伤水平更高。豚鼠绒毛膜羊膜炎导致母体和胎儿促炎性细胞因子的增加以及胎儿脑损伤的发生,与脑瘫相似。

著录项

  • 作者单位

    Queen's University (Canada).;

  • 授予单位 Queen's University (Canada).;
  • 学科 Biology Anatomy.;Health Sciences Obstetrics and Gynecology.;Health Sciences Pathology.
  • 学位 M.Sc.
  • 年度 2003
  • 页码 68 p.
  • 总页数 68
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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