MAGNESIUM SULFATE AND PRETERM FETAL BRAIN INJURY

胎儿缺氧，即使是在怀孕早期， 严重的神经和行为缺陷，可能是 与脑瘫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， 神经营养因子在大脑发育中的作用。 L-谷氨酸（Glu）， 兴奋性氨基酸，在大脑发育中起着关键作用。 一些 有证据表明，Glu数量的改变可以产生 异常的生长促进和可能的神经元死亡。 在体外 研究支持这一建议，直到最近， 确定缺氧是否会改变完整胎儿大脑中Glu的释放。与 最后，我们开发了宫内胎儿微透析新技术， 将微透析探针植入胎羊大脑中 皮层 使用人工恢复的仪器妊娠绵羊， Glu的释放可以在基础和病理条件下测量， 在没有麻醉剂的情况下。 另一个临床问题是， 高危妊娠在病理生理过程中可能影响胎儿健康 侮辱。 一种这样的药物是硫酸镁（MgSO 4），其通常是 用于早产儿和先兆子痫的产妇。 这样的患者往往 有持续增加的风险经历一个发作的胎儿 缺氧 之前的实验研究表明，MgSO 4可能 在胎儿/母体压力期间对胎儿产生负面影响。 然而，在这方面， 镁离子可以与Glu受体相互作用， 胎儿大脑缺氧引起的谷氨酸释放增加。 本提案的总体目标是研究MgSO 4的作用 在急性缺氧发作期间，在子宫内使用 微透析 我们将检验两个假设：1）MgSO 4的存活率 早产儿急性缺氧后MgSO 4的变化 早产儿急性缺氧时大脑皮质谷氨酸释放 通过定性组织学研究，我们还将试图确定 硫酸镁改变了胎儿缺氧性神经损伤的模式。 MgSO 4通常用于高危妊娠，尽管其作用 胎儿在压力下的变化还没有得到很好的表征。 的 本研究旨在模拟MgSO 4的临床产科应用： 例如一名接受硫酸镁治疗的早产儿， 继发于脐带闭塞的危害。 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 可用于评估MgSO 4是否具有药理学潜力 在胎儿缺氧期间进行干预，或者相反，是否使用 MgSO 4在有胎儿缺氧风险的产妇中， 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.