CEREBROVASCULAR EFFECTS OF PRENATAL ALCOHOL

描述：（改编自申请人摘要）胎儿脑损伤导致 母亲酗酒是智力迟钝的主要原因之一 但子宫内酒精暴露的机制 对胎儿大脑发育和功能的不利影响在很大程度上是未知的。的 研究人员最近证实， 暴露于慢性母体酒精的新生绵羊的血管舒张 妊娠早期的中毒基于这些和其他支持 研究发现，他们提出了一个假设，即在子宫内接触酒精 影响脑血管的发育和功能， 随之而来的血管异常可能有助于脑血管病的发病机制， 与胎儿酒精暴露有关的损伤。 该提案的目的是进一步描述脑血管疾病的特征， 和神经病理学影响的慢性胎儿酒精暴露在绵羊， 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方法， 和免疫细胞化学，以解决以下目标： 目的#1：确定慢性母亲酒精中毒是否在第一次 或中期妊娠改变胎儿脑血管对体内缺氧的反应 在怀孕后期。 目的#2：比较反复缺氧损伤对大鼠脑组织的神经病理学影响。 先前在子宫内暴露于酒精或盐水的胎儿。 目的#3：确定产前酒精暴露改变 脑血管反应性通过检查脑血管的成熟 网络和研究脑血管舒张功能的密度和表达， 物质. 目的4：确定产前酒精是否会改变脑血管反应性 通过测试插管、加压的胎儿和成人的反应， 绵羊小动脉血管活性物质。 目的#5：确定怀孕期间是否有产前酒精暴露 改变胎儿或成人脑血管对急性酒精中毒的反应。 这些研究的结果将提供有关 胎儿脑血管异常对脑损伤的影响 与胎儿酒精暴露有关，并将导致 对吸毒孕妇的围产期预防和/或治疗战略 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.