VESTIBULAR-CEREBROVASCULAR INTERACTIONS IN HUMANS

描述(申请人提供)：跌倒是老年人发病的主要原因，每年导致3600万人次住院，费用超过100亿美元。虽然许多跌倒的原因尚不清楚，但晕厥和直立性低血压是重要因素。由于前庭激活在立位应激期间对血压的调节具有积极作用，而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会导致立位时血压调节的受损，这反过来又会导致脑灌注量减少和晕厥。前庭激活对脑血流量有直接影响的先前证据表明，前庭输入影响脑血管对直立位的反应。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起到前馈机制的作用，导致脑血管扩张，以补偿直立姿势导致的脑灌流压力的下降。我们提出了两个具体的目标来解决这一假设：1)确定倾斜在俯仰(矢状面)和滚动面(侧)对年轻人和老年人(有或没有前庭功能障碍)的脑血流和脑自动调节的影响。这一目标将通过被动倾斜受试者，眼睛在俯仰和滚转平面上从水平直立姿势闭合到80度直立来实现；以及2)确定迷路缺陷住院患者和健康对照组在离心机分离过程中耳石刺激对脑血流的影响。这一目标将通过在短臂离心机上改变迷路缺陷患者和性别和年龄匹配的健康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。这项工作可能会导致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将老年人的脑低灌注、晕厥和跌倒降至最低的方法。

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.