VESTIBULAR-CEREBROVASCULAR INTERACTIONS IN HUMANS

描述（由申请人提供）：福尔斯是老年人发病的主要原因，每年有3600万人就诊，费用超过100亿美元。虽然许多福尔斯跌倒的原因仍然无法解释，但晕厥和直立性低血压是重要因素。由于前庭激活已被证明在直立应激期间的血压调节中具有积极作用，并且前庭功能随着年龄>60岁而降低，因此我们假设老年人的前庭功能减退导致直立期间血压调节受损，这反过来又导致脑灌注不足和晕厥。以前的证据表明，前庭激活对脑血流量有直接影响，提示前庭输入影响脑血管对体位的反应。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立位耐力的影响。我们的一般假设是，耳石介导的前庭输入作为一个前馈机制，导致脑血管舒张，以补偿脑灌注压下降引起的直立姿势。我们提出了两个具体的目标来解决这个假设：1）确定倾斜（矢状面）和滚动（横向）平面对年轻和老年受试者（有和没有前庭功能障碍）的脑血流和脑自动调节的影响。这一目的将通过在俯仰和滚动平面中将受试者从水平闭眼被动倾斜到80度直立姿势来实现;和2）确定在离心过程中耳石刺激对脑血流量的影响，在脑啡肽缺陷住院患者和健康对照中。这一目标将通过改变短臂离心机上的谷胱甘肽缺陷患者和健康的性别和年龄匹配的对照的旋转半径来实现。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。这项工作可能会导致新的方法来诊断那些有福尔斯风险的人，以及训练前庭系统以减少老年人脑灌注不足，晕厥和福尔斯的方法。

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.