# Development of a clinically-relevant test for assessment of cerebral vascular function

> **NIH NIH F32** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $22,409

## Abstract

PROJECT SUMMARY
The overall goal of this research project is to develop a test of cerebral vascular function, and provide
mechanistic insight into the extent to which the myogenic, neurogenic, and shear-mediated responses contribute
to the regulation of the cerebral vasculature. Cerebrovascular disease is the 5th leading cause of death, as well
as being a major cause of cognitive impairment and disability in middle-aged to older adults. Understanding the
relationship between aging and cerebrovascular function is essential to the development of therapeutic
interventions that will improve quality of life and reduce the risk of cerebrovascular events. There are currently
no preclinical tools for prediction of future cerebrovascular disease/events in healthy humans; the proposed
study aims to address this knowledge gap. The central hypothesis is that our test of “Cerebral-Vascular
Function” will elicit a vasodilatory stimulus, which will be reduced in healthy older subjects, and chronic smokers,
and that impairment in these responses will be associated with impaired peripheral vascular regulation and with
reduced cerebral vascular reactivity to CO2. A secondary hypothesis is that that blockade of myogenic and
neurogenic responses to the “Cerebral-Vascular Function” test will facilitate assessment of the endothelial shear-
stress dependent mechanism of cerebral blood flow regulation. We will address these hypotheses in two broad
Specific Aims: 1) assess the responses to the Cerebral-Vascular Function test , and compare responses with
a classic test of Cerebral Vascular Reactivity to CO2, and the Peripheral-Vascular Reactivity tests in healthy
young subjects, and subjects known to have impaired systemic vascular function, (older healthy subjects, and
chronic smokers), and; 2) determine the relative contribution of endothelial-mediated hyperemia from myogenic
and neurogenic control of cerebral blood flow. Human subjects will be recruited to address these aims, by
adapting the peripheral flow-mediated dilation (FMD) approach of ischemia-reperfusion to the cerebral
vasculature by use of lower body negative pressure (LBNP). LBNP (-60 mmHg) will be applied to induce an
“ischemic” stress to the cerebral tissue; rapid release of this stress will elicit shear stress induced cerebral
vasodilation. Reactive hyperemia in the intracranial and extracranial arteries will be assessed via calculation of
the peak and area under the curve for each response as an index of resistance vessel function. Independently,
FMD in the brachial and femoral arteries will be assessed. The rationale for the proposed research is to develop
a clinically-relevant test for assessment of cerebral vascular function and identify a mechanism for the previously
observed increase in cerebral blood flow to simulated “ischemia-reperfusion” stress. The approach is innovative
as it may provide evidence that cerebral reactive hyperemia is a novel methodological approach and a valid
stimulus to asses...

## Key facts

- **NIH application ID:** 10227260
- **Project number:** 5F32HL144082-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Alexander Rosenberg
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $22,409
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-08-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10227260

## Citation

> US National Institutes of Health, RePORTER application 10227260, Development of a clinically-relevant test for assessment of cerebral vascular function (5F32HL144082-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10227260. Licensed CC0.

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