VESTIBULAR-CEREBROVASCULAR INTERACTIONS IN HUMANS

描述（由申请人提供）：跌倒是老年人发病的主要原因，每年导致3 600万人次到医院就诊，费用超过100亿美元。虽然许多跌倒的原因仍然不明，晕厥和直立性低血压是重要的因素。由于前庭激活已被证明在直立应激时对血压的调节中起积极作用，并且前庭功能随着年龄的增长而下降，我们假设老年人前庭功能低下导致直立时血压调节受损，从而导致脑灌注不足和晕厥。前庭激活对脑血流有直接影响的先前证据表明，前庭输入影响脑血管对直立的反应。本研究的目的是研究前庭输入在脑血流调节中的作用以及这些输入对直立耐受性的影响。我们的一般假设是耳石介导的前庭输入作为前馈机制导致脑血管舒张，以补偿直立姿势引起的脑灌注压下降。我们提出了两个具体的目标来解决这一假设：1)确定俯仰（矢状面）和俯仰（侧）平面的倾斜对年轻和老年受试者（有或没有前庭功能缺陷）脑血流和大脑自动调节的影响。这一目标将通过被动倾斜受试者，闭上眼睛，从水平到俯仰和翻滚平面上的80度直立姿态来实现；2)确定离心时耳石刺激对迷路缺陷住院患者和健康对照者脑血流量的影响。这一目标将通过在短臂离心机上改变迷路缺陷患者和健康的性别和年龄相匹配的对照组的旋转半径来实现。这些研究结果将为前庭输入在脑血管调节中的作用提供直接证据。这项工作可能会带来新的方法来诊断那些有跌倒风险的人，以及训练前庭系统以减少大脑低灌注、晕厥和老年人跌倒的方法。

DESCRIPTION (provided by applicant): Falls are a leading cause of morbidity in the elderly, resulting in 36 million hospital visits per year, at a cost in excess of $10 billion. While the cause of many falls remains unexplained, syncope and orthostatic hypotension are important factors. Since vestibular activation has been shown to have an active role in the regulation of blood pressure during orthostatic stress, and vestibular function decreases with age >60 years, we hypothesize that vestibular hypo-function in the elderly results in impaired regulation of blood pressure during orthostasis, which in turn results in cerebral hypo-perfusion and syncope. Previous evidence that vestibular activation has direct effects on cerebral blood flow suggests that vestibular inputs affect the cerebrovascular response to orthostasis. The goal of this research is to examine the role of vestibular inputs in cerebral blood flow regulation and the effect of these inputs on orthostatic tolerance. Our general hypothesis is that otolith-mediated vestibular inputs act as a feed forward mechanism causing cerebral vasodilatation, to compensate for the decrease in cerebral perfusion pressure caused by the upright posture. We propose two specific aims to address this hypothesis: 1) Determine the effect of tilts in the pitch (sagittal) and roll (lateral) planes on cerebral blood flow and cerebral auto-regulation in young and older subjects (with and without vestibular deficits). This aim will be accomplished by passively tilting subjects with eyes closed from a horizontal to 80 degree upright posture in the pitch and roll planes; and 2) Determine the effect of otolith stimulation during centrifugation on cerebral blood flow in labyrinthine defective inpatients and healthy controls. This aim will be accomplished by varying the radius of rotation of labyrinthine-defective patients and healthy gender- and age-matched controls on a short arm centrifuge. The results of these studies will provide direct evidence on the role of vestibular inputs in cerebrovascular regulation. This work may lead to new methods to diagnose those at risk for falls, as well as ways to train the vestibular system to minimize cerebral hypo-perfusion, syncope, and falls in the elderly.