FOREBRAIN PLASTICY IN HYPERTENSION

前脑可塑性的L-Lypertenslon计划是一个新的多学科的研究计划，重点是 支配关键前脑中枢之间神经体液相互作用的基本生物学过程 和心血管系统。该计划的长期目标是阐明这些因素的作用 高血压的发病机制和随之而来的终末器官损害，特别是 脑血管受损。PPG的中心主题侧重于穹隆下器的作用， 室周器官之一，和下丘脑室旁核(PVN)，主要输出 SFO在交感神经过度活动和荷尔蒙释放中的途径 压力。中心假设是，在缓慢发展的高血压患者中，存在适应性改变。 (神经可塑性)在SFO-PVN轴上发生适应不良，并为神经体液奠定基础 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 使用临床相关的高血压小鼠模型的中心假说的特定方面 全身输注小剂量血管紧张素II(Ang11)。项目1将检查下行信令 血管紧张素转换酶诱导高血压的机制，着重于前列腺素作为 重要的中介机构。项目2将审查关键的结构和功能不适应机制 室旁核，使神经体液功能障碍成为高血压发生的基础。项目3 将重点放在PVN的结构和功能修改上，这是导致增加的 更年期女性对高血压的易感性。项目4将讨论SFO-PVN轴在 高血压对重要的脑血管调节机制的有害影响 有足够的血流输送到大脑。这些项目得到了一个管理核心--分子 生物学--鼠芯、神经解剖学核心和射电核心。中国的一大强项 每个项目都结合了分子、神经解剖学、神经生理学和心血管 实现所述目标的综合方法。这些项目由一群高度互动的 成熟的研究人员，并发挥彼此的优势，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 预计该方案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.