Jorge M. Serrador, Ph.D. - US grants

[unreadable] 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. [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Motion sickness is a debilitating condition that affects a wide range of individuals in both daily life and in pathological conditions. While it is widely seen in many clinical settings, it remains difficult to objectively evaluate and treat. Recent work by our group has found a connection between decreases in brain blood flow and the development of nausea. Based on this and other research, the question arises as to what role does decreased brain blood flow play in the development of motion sickness. The overall goal of this work is to determine the relationship between brain blood flow and the development of motion sickness. To answer this question we are proposing the following specific aims: 1) Determine if decreases in brain blood flow can accurately predict the onset of motion sickness;2) Determine if maintaining end tidal CO2 during a motion stimulus eliminates the reduction in cerebral blood flow due to increased ventilation and extends time to symptoms or eliminates the development of motion sickness. To achieve this goal we will use off vertical axis rotation at two rotation speeds, one which has been shown to be very nauseogenic and one which is easily tolerated. We can compare the response of these two paradigms to determine if brain blood flow decreases prior to motion sickness symptoms. In addition we can add inspired CO2 to maintain arterial CO2 and improve brain blood flow during rotation. The findings of this work could translate into significant clinical and research advancements. Using brain blood flow during desensitization training could reduce aversive events and greatly enhance and broaden the clinical applications of motion sickness treatments. The development of an objective measure of motion sickness would allow for better understanding of the mechanisms. PUBLIC HEALTH RELEVANCE: The goal of this research is to understand the relationship between brain blood flow and the development of motion sickness. By understanding how reductions in cerebral blood flow are related to the development of nausea, new diagnostic and treatment methods may be developed.