MAGNESIUM SULFATE AND PRETERM FETAL BRAIN INJURY

即使在怀孕早期，胎儿缺氧的发作也可能产生 出生后生活中严重的神经和行为缺陷，可能是 与脑性瘫痪等疾病的病因学有关。这些 赤字可能是由于数量或功能的改变造成的 脑发育中的神经营养因子(S)。L-谷氨酸、安非他明 兴奋性氨基酸在大脑发育中起着关键作用。一些人 有证据表明，谷氨酸含量的变化可以产生 异常的生长促进和可能的神经元死亡。而在体外 研究支持这一提议，直到最近才有可能 确定缺氧是否会改变完整胎儿大脑中谷氨酸的释放。到那时候 最后，我们开发了宫内胎儿微透析的新技术，在 胎羊脑内植入了哪些微透析探头 大脑皮层。使用通过手术恢复的妊娠绵羊， 谷氨酸的释放可在基础状态和病理状态下测量。 在没有麻醉剂的情况下。 另一个临床问题是，使用的药物治疗在 高危妊娠可能会在病理生理过程中影响胎儿的健康 侮辱。一种这样的药物是硫酸镁(镁)，它通常是 用于早产儿和先兆子痫产妇。这类患者经常 有持续增加的经历胎儿心脏病发作的风险 缺氧。先前的实验研究表明，硫酸镁可能会 在胎儿/母亲应激期间对胎儿产生负面影响。然而， 镁离子可以与谷氨酸受体相互作用，并可能实际上保护 胎儿大脑从低氧诱导的谷氨酸释放增加。 这项提案的总体目标是调查硫酸镁的行为。 宫内应用对早产儿急性缺氧发作的影响 微透析。我们将检验两个假设：1)硫酸镁使存活率变差 急性缺氧对早产儿的影响；2)硫酸镁的变化 急性缺氧后早产儿大脑皮质谷氨酸的释放。 通过定性的组织学研究，我们还将尝试确定 硫酸镁改变胎儿缺氧性神经损伤的模式。 硫酸镁通常用于高危妊娠，尽管它的作用 在胎儿期间的应激反应还没有得到很好的描述。这个 本研究旨在模拟临床产科使用硫酸镁： 例如，服用硫酸镁的早产产妇经历了突然的胎儿 继发于脐带闭塞的损害。 这项研究的完成将产生关于 缺氧和硫酸镁对早产儿的影响这些结果将 有助于评估硫酸镁是否具有潜在的药理作用 干预期间胎儿缺氧，或反之，是否使用 有胎儿缺氧风险的产妇应给予硫酸镁 重新评估。

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.