CEREBROVASCULAR EFFECTS OF PRENATAL ALCOHOL

描述：(改编自申请者的摘要)造成的胎儿脑损伤 母亲酗酒是导致智力低下的主要原因之一 在美国，但宫内酒精暴露的机制 对胎儿大脑发育和功能的负面影响在很大程度上是未知的。这个 研究人员最近证实了减弱的低氧；大脑 慢性母体酒精对新生绵羊血管的扩张作用 怀孕前三个月中毒。基于这些和其他支持 研究发现，他们提出了一种假设，即在子宫内接触酒精 影响脑血管的发育和功能，而 随之而来的血管异常可能参与脑部的发病。 与胎儿酒精接触有关的损害。 这项建议的目的是进一步描述脑血管的特征 和慢性胎儿酒精暴露对绵羊的神经病理影响，以及 评估这些影响的潜在机制和后果。他们 将使用体内和体外生理学方法以及神经病理学 和免疫细胞化学，以解决以下目标： 目的1：确定慢性母体酒精中毒是否首先发生在 妊娠中期改变胎儿脑血管对体内缺氧的反应 在怀孕后期。 目的#2：比较反复低氧侮辱对大鼠神经病理的影响 胎儿在宫内曾接触过酒精或生理盐水。 目标3：确定产前酒精暴露改变的机制 通过检测脑血管成熟度来检测脑血管反应性 并通过对脑血管舒张剂密度和表达的研究 物质。 目的#4：确定产前酒精是否会改变脑血管反应性 在体外通过测试插管、加压胎儿和成人的反应 绵羊小动脉对血管活性物质的影响。 目的5：确定孕期有无产前酒精暴露 改变胎儿或成人对急性酒精中毒的脑血管反应。 这些研究的结果将提供关于 胎儿脑血管异常在脑损伤中的作用 与胎儿酒精暴露有关，并将导致 为孕妇提供围产期预防和/或治疗策略 酒精。

DESCRIPTION: (adapted from applicant's abstract) Fetal brain damage resulting from maternal alcohol abuse is one of the leading causes of mental retardation in the United States and yet the mechanisms by which in utero alcohol exposure adversely affects fetal brain development and function are largely unknown. The investigators have recently demonstrated attenuated hypoxic; cerebral vasodilation in newborn sheep which were exposed to chronic maternal alcohol intoxication in the first trimester. Based on these and other supportive findings, they have developed the hypothesis that in utero alcohol exposure affects the development and function of cerebral blood vessels, and that the consequent vascular abnormalities may contribute to the pathogenesis of brain damage associated with fetal alcohol exposure. The objective of this proposal is to further characterize the cerebrovascular and neuropathological effects of chronic fetal alcohol exposure in sheep, and to evaluate potential mechanisms for and consequences of these effects. They will use in vivo and in vitro physiological methods as well as neuropathology and immunocytochemistry to address the following aims: Aim #1: To determine whether chronic maternal alcohol intoxication in the first or second trimester alters fetal cerebrovascular responses to hypoxia in vivo later in pregnancy. Aim #2: To compare the neuropathologic effects of repeated hypoxic insults in fetuses previously exposed to either alcohol or saline in utero. Aim #3: To determine mechanisms whereby prenatal alcohol exposure alters cerebrovascular reactivity by examining the maturation of the cerebral vascular network and by studying the density and expression of cerebral vasodilatory substances. Aim #4: To determine whether prenatal alcohol alters cerebrovascular reactivity in vitro by testing the responses of cannulated, pressurized fetal and adult sheep arterioles to vasoactive substances. Aim #5: To determine whether prior prenatal alcohol exposure during pregnancy alters fetal or adult cerebrovascular responses to acute alcohol intoxication. Results from these studies will provide important new information regarding the contribution of fetal cerebrovascular abnormalities to the brain damage associated with fetal alcohol exposure and will lead to the development of perinatal preventive and/or therapeutic strategies for pregnant women who use alcohol.