Understanding the contribution of altered cerebrovascular function to the pathology and clinical symptoms of Huntington disease

项目总结/摘要：该提案旨在建立病理生理机制， 建立了神经血管功能障碍、神经功能缺损和脑变性之间的关系， 亨廷顿病（HD）。它建立在我们对神经血管改变的重要性的不断增长的理解之上。 在神经变性，包括在HD，并利用临床和神经影像学专业知识，以及 一个良好表征的HD基因扩增个体队列的可用性。AIM 1检查十字架- 脑血管反应性（CVR）的局部变化并检验CVR受损的假设 引发局灶性脑萎缩目的2测试特定假设，即灌注受损（CBF）发生在HD中， 与局部改变的CVR有关。目的3评价脊髓损伤后神经血管的纵向变化， 这些变化的位置和严重程度与临床进展率和脑损害率之间的因果关系 萎缩这些目标的成功实现将为理解关键血管病变奠定坚实的基础。 可能影响进展和HD的机制，并将神经血管机制确立为重要靶点 用于未来的HD临床药物试验

PROJECT SUMMARY/ABSTRACT: This proposal seeks to establish the pathophysiological mechanisms that establish a relationship between neurovascular dysfunction, neurological impairment and brain degeneration in Huntington’s disease (HD). It builds on our growing understanding of the important of neurovascular alterations in neurodegeneration, including in HD, and takes advantage of clinical and neuroimaging expertise as well as the availability of a well-characterized cohort of HD gene-expanded individuals. Aim1 examines the cross- sectional regional changes in cerebrovascular reactivity (CVR) and tests the hypothesis that impaired CVR triggers focal brain atrophy. Aim 2 tests the specific hypothesis that impaired perfusion (CBF) occurs in HD and is associated with regionally altered CVR. Aim 3 evaluates the longitudinal neurovascular changes and the causal relationship between location and severity of these changes with rates of clinical progression and of brain atrophy. Successful achievement of these aims will establish a strong foundation for understanding key vascular mechanisms that may affect progression and HD and establish neurovascular mechanisms as important targets for future clinical drug trials in HD