MAGNESIUM SULFATE AND PRETERM FETAL BRAIN INJURY

硫酸镁与早产胎儿脑损伤

• 批准号: 2026549
• 负责人: JAMES D REYNOLDS
• 金额: $ 7.7万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-24 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2026549
• 关键词: cerebral ischemia /hypoxia; embryo /fetus; embryo /fetus drug adverse effect; embryo /fetus hypoxia; glutamates; magnesium; microdialysis; neuroprotectants; neurotransmitter transport; sheep; sulfates

An episode of fetal hypoxia, even early on in pregnancy, can produce severe neurologic and behavioral deficits in postnatal life and may be involved in the etiology of conditions such as cerebral palsy. These deficits may result from alterations in the amount or function of neurotropic factor(s) in developing brain. L-glutamate (Glu), an excitatory amino acid, plays a key role in brain development. Some evidence suggests that alterations in the amount of Glu can produce aberrant growth promotion and possibly neuronal death. While in vitro studies support this proposal, until recently it has not been possible to determine if hypoxia alters Glu release in the intact fetal brain. To that end, we developed the novel technique of in utero fetal microdialysis, in which microdialysis probes are implanted into the fetal sheep cerebral cortex. Using the surgically-recovered instrumented pregnant sheep, the release of Glu can be measured under basal and pathologic conditions in the absence of anesthetic agents. A further clinical concern is that pharmacologic treatments employed in high-risk pregnancy may affect fetal well-being during pathophysiologic insult. One such drug is magnesium sulfate (MgSO4), which is commonly used in premature and preeclamptic parturients. Such patients often have an ongoing increased risk of experiencing an episode of fetal hypoxia. Previous experimental studies have suggested that MgSO4 may impact negatively on the fetus during fetal/maternal stress. However, magnesium ion can interact at Glu receptors and may actually protect the fetal brain from a hypoxia-induced increase in Glu release. The overall aim of this proposal is to investigate the actions of MgSO4 on the preterm fetus during an episode of acute hypoxia, using in utero microdialysis. We will test two hypotheses: 1) MgSO4 worsens survival of the preterm fetus following acute hypoxia; and 2) MgSO4 changes cerebral cortical Glu release in preterm fetus following acute hypoxia. With qualitative histologic studies, we will also attempt to determine if magnesium sulfate alters the pattern of fetal hypoxic neurologic injury. MgSO4 is commonly used in high-risk pregnancies even though its action in the fetus during stress have not been well characterized. The present study is designed to mimic the clinical obstetrical use of MgSO4: e.g. a preterm parturient receiving MgSO4 who experiences sudden fetal compromise secondary to umbilical cord occlusion. Completion of this study will yield important new information about the effects of hypoxia and MgSO4 on the preterm fetus. These results will be useful in assessing if MgSO4 has potential as a pharmacologic intervention during fetal hypoxia, or, conversely, whether the use of MgSO4 in parturients at risk for an episode of fetal hypoxia should be re-evaluated.

即使在怀孕的早期，胎儿缺氧的发作也会产生 产后生活中严重的神经系统缺陷，可能是 参与脑瘫等疾病的病因。 这些 赤字可能是由于数量或功能的变化而导致的 发育中的大脑中的神经性因子。 l-glutamate（glu），an 兴奋性氨基酸在大脑发育中起关键作用。 一些 有证据表明，GLU量的改变可以产生 异常增长促进，可能是神经元死亡。 在体外 研究支持该建议，直到最近才有可能 确定缺氧是否会改变GLU在完整的胎儿大脑中的释放。为此 最后，我们开发了子宫胎儿微透析中的新技术 哪些微透析探针被植入胎儿绵羊大脑 皮质。 使用外科手术的仪器怀孕绵羊， GLU的释放可以在基础和病理下测量 没有麻醉剂的情况。 进一步的临床问题是在 高危妊娠可能会影响病理生理期间的胎儿健康 侮辱。 一种这样的药物是硫酸镁（MGSO4），通常是 用于早产和先兆分类量。 这样的患者经常 经历胎儿发作的风险持续增加 缺氧。 先前的实验研究表明MGSO4可能 在胎儿/孕妇应激期间对胎儿的影响。 然而， 镁离子可以在GLU受体上相互作用，实际上可以保护 缺氧引起的GLU释放增加的胎儿大脑。 该提案的总体目的是调查MGSO4的行为 在急性缺氧发作期间的早产胎儿，在子宫内使用 微透析。 我们将检验两个假设：1）MGSO4使生存恶化 急性缺氧后的早产胎儿； 2）MGSO4改变 急性缺氧后，早产胎儿的脑皮质GLU释放。 通过定性组织学研究，我们还将尝试确定是否是否 硫酸镁改变了胎儿缺氧神经系统损伤的模式。 MGSO4通常在高危妊娠中使用 在压力期间，胎儿没有得到很好的特征。 这 目前的研究旨在模仿MGSO4的临床产科使用： 例如一个早产偏向于接收MGSO4，经历了突然的胎儿 继发于脐带阻塞的妥协。 这项研究的完成将产生有关 缺氧和MGSO4对早产胎儿的影响。 这些结果将会 在评估MGSO4是否具有药理学的潜力方面有用 胎儿缺氧期间的干预，或者相反，是否使用 MGSO4在有胎儿缺氧发作风险的分离率中应为 重新评估。