Stroke is the third leading cause of death and the leading cause of disability in older people. Our long-term goal is to determine the effects of stroke on cerebral vasoregulation. Our hypotheses are as follows: Hypothesis 1: The older adults with ischemic stroke have impaired cerebral vasoregulation, rendering cerebral blood flow dependent on blood pressure (BP). Therefore, we will evaluate cerebral vasoregulation in response to CO2 and BP challenges to determine whether cerebral blood flow is higher with increased perfusion pressure in stroke-hypertensive than stroke-normotensive subjects. Hypothesis 2: Autonomic BP control is altered after stroke. Therefore, activities of daily living may induce orthostatic hypotension (OH), posing a risk of cerebral hypoperfusion. We will evaluate cerebral blood flow and BP responses during orthostatic stress to identify subjects with OH, who may develop cerebral hypoperfusion. Hypothesis 3: The distribution of impaired vasoreactivity extends beyond the infarct site into surrounding areas of gray and white matter affecting different vascular territories. We will quantify cerebral blood flow in gray and white matter using arterial spin labeling at 3 Tesla MRI and evaluate the distribution of vasoreactivity during hypo-and hypercapnia. We will use T2-weighted FLAIR MRI to measure the distribution of infarcts and white matter changes and compare it to the cerebral blood flow maps. We will study 60 subjects (>60 years old, normotensive and hypertensive with the first hemispheric large vessel infarct affecting <1/3 of middle cerebral artery territory [MCA], >6 months post-stroke) and compare them to 60 normotensive and hypertensive subjects without stroke. To evaluate vasoreactivity to CO2 stimulus we will measure blood flow velocity (BFV) in both MCAs during hypo- and hypercapnia using transcranial Doppler ultrasound. Cerebral vasoreactivity to BP stimulus will be evaluated from BFV responses to Valsalva maneuver, sit-to-stand test and head-up tilt. We expect to find that with impaired vasoregulation cerebral blood flow becomes dependent on perfusion pressure. Therefore, in older adults with stroke, OH may trigger cerebral hypoperfusion and cause further damage to an already compromised cerebrovascular bed. The results of this study may improve our understanding of optimal BP targets for the maintenance of cerebral perfusion in elderly people with stroke.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Clinical Neuroscience and Disease Study Section (CND)
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Jacobs, Tom P
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Beth Israel Deaconess Medical Center
United States
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