FOREBRAIN PLASTICY IN HYPERTENSION

L-lypertenslon计划的前脑可塑性是一个新的多学科研究计划，重点是 控制关键前脑中心之间神经体液相互作用的基本生物过程 和心血管系统。该计划的长期目标是阐明这些 在高血压的发病机制和随后的终末器官损害，特别是 脑血管损伤PPG的中心主题关注穹窿下器官（SFO）的作用， 室周器官之一，下丘脑室旁核（PVN），主要输出 SFO的途径，在交感神经过度活跃和激素释放的基础上增加血液 压力中心假设是在缓慢发展的高血压中存在适应性改变 （神经可塑性）在SFO-PVN轴，变成适应不良，并设置了阶段的神经体液 调节失调导致高血压和脑血管功能障碍。每个项目都涉及一个 中心假设的特定方面，使用临床相关的高血压小鼠模型， 全身输注低剂量的血管紧张素II（AngII）。项目1将检查下行信令 SFO中AngII诱导高血压的机制，重点是前列腺素类作为 重要的中介。项目2将研究关键的结构和功能适应不良的机制， PVN，其使神经体液功能障碍成为高血压发展的基础。项目3 将集中在PVN的结构和功能修饰，负责增加 绝经期女性对高血压的易感性。项目4将解决SFO-PVN轴在以下方面的作用： 高血压对重要的脑血管调节机制的有害影响， 足够的血流输送到大脑。该项目由一个行政核心，一个 生物学-小鼠核心，神经解剖学-lmaaina核心和无线电遥测核心。一个主要的优势， 每个项目都结合了分子，神经解剖学，神经生理学和心血管 采取综合办法实现既定目标。这些项目由一个高度互动的小组领导， 已建立的研究人员，并建立在对方的优势，使一个项目的科学产出， 与其他项目中提出的研究协同作用。因此，集体科学成果 预计该计划的总价值将大于其各个组成部分的总和。

The Forebrain Plasticity in l-lypertenslon Program is a new multidisciplinary research program focused on the fundamental biological processes governing the neurohumoral interaction between key forebrain centers and the cardiovascular system. The long-term objective of the program is to elucidate the role of these centers in the pathogenesis of hypertension and in the ensuing end-organ damage, particularly cerebrovascular damage. The central theme of the PPG focuses on the role of the subfornical organ (SFO), one of the circumventricular organs, and the hypothalamic paraventricular nucleus (PVN), the main output pathway of the SFO, in the sympathetic overactivity and hormonal release underlying the increase in blood pressure. The central hypothesis is that in slow-developing hypertension there are adaptive modifications (neuroplasticity) in the SFO-PVN axis that turn maladaptive, and set the stage for the neurohumoral dysregulation driving the hypertension and the cerebrovascular dysfunction. Each project addresses a specific facet of the central hypothesis using a clinically relevant mouse model of hypertension produced by systemic infusion of a low dose of angiotensin II (Angll). Project 1 will examine the downstream signaling mechanisms in SFO by which Angll induces the hypertension, focusing on the role of prostanoids as essential intermediaries. Project 2 will examine critical structural and functional maladaptive mechanisms in the PVN, which enable the neurohumoral dysfunction underlying the development of hypertension. Project 3 will focus on the structural and functional modifications in the PVN that are responsible for the increased susceptibility to hypertension in menopausal females. Project 4 will address the role of the SFO-PVN axis in the deleterious effects of hypertension on vital cerebrovascular regulatory mechanisms that assure an adequate blood flow delivery to the brain. The Projects are supported by an Administrative Core, a Molecular Biology-Mouse Core, a Neuroanatomv-lmaaina Core and a Radiotelemetrv Core. A major strength of the program is that each project combines molecular, neuroanatomical, neurophysiological and cardiovascular integrative approaches to achieve the stated goals. The projects are led by a highly interactive group of established investigators and build on each other's strengths so that the scientific output of one project interacts synergistically with the research proposed in other projects. Thus, the collective scientific outcome of the Program is anticipated to be greater than the sum of its individual components.