The Effects of Alcohol on Fetal Cerebral Blood Flow

描述(申请人提供)：本建议的目的是调查酒精暴露对妊娠晚期绵羊脑血流的影响。神经缺陷是母亲酗酒最具破坏性的后果。尽管有大量关于这一主题的研究文献，但令人惊讶的是，人们对酒精作用的潜在机制知之甚少。一种可能的机制可能与胎儿脑血流有关，因为神经血管对正常的神经发育非常重要。这一提议产生的数据将有助于我们进一步了解胎儿酒精引起脑损伤的机制。这些目标将通过使用绵羊模型系统在两个具体目标中实现。《特定目标1》将检验反复饮酒会对胎儿脑血流产生不利影响的假设。《特定目的2》将测试反复酒精暴露会影响神经血管对急性酒精暴露的反应性这一假设。这些实验将使用绵羊模型系统进行，以保持母体/胎儿单位的完整。将使用放射性标记的微球测量子宫内胎羊的局部血流量。了解酒精在发育过程中的作用将有助于指导未来的预防和治疗策略。

DESCRIPTION (provided by applicant): The purpose of this proposal is to investigate the effects of alcohol exposure on cerebral blood flow during the third trimester in sheep. Neurological deficits are the most devastating consequences of maternal alcohol abuse. In spite of the huge research literature on this subject, surprisingly little is known about the mechanisms underlying alcohol's effects. One possible mechanism may be associated with fetal cerebral blood flow, since the neurovasculature is so important for proper neurodevelopment. The data generated from this proposal will help to further our understanding of the mechanisms of fetal alcohol-induced brain damage. The goals will be addressed in two specific aims using a sheep model system. SPECIFIC AIM #1 will test the hypothesis that repeated alcohol exposure will adversely affect fetal cerebral blood flow. SPECIFIC AIM #2 will test the hypothesis that repeated alcohol exposure will affect the neurovascular responsiveness to acute alcohol exposure. These experiments will be performed using the sheep model system in order to maintain an intact maternal/fetal unit. Regional blood flow will be measured in fetal sheep in utero using radiotabelled microspheres. Understanding alcohol's effects during development will be helpful in the future for guiding prevention and therapy strategies.