# The impact of microvascular (dys)regulation on cerebral flow and oxygen heterogeneity

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2021 · $626,919

## Abstract

ABSTRACT
As the cerebral cortex has no energy reserve, it requires a tight coupling between the supply of
nutrients and oxygen and the metabolic demand of the tissue. Small blood vessels, from which
nutrients and oxygen are supplied, are hypothesized to be highly heterogeneous in structure
and function. The nature and role of this heterogeneity under physiological conditions and how it
may lead to pathologies is not fully understood. The size and complexity of the microcirculation
and lack of technologies capable of measuring dynamics of the microcirculation have hindered
progress. Sophisticated imaging tools with high spatiotemporal resolution are necessary to
study the dynamic heterogeneity of the capillary network. This is particularly important for
studying a new dynamic phenomenon within the microvasculature which we have recently
observed and implicated in brain disease. Specifically, temporary interruptions of blood flow in
individual cerebral capillaries (i.e. RBC stalls) are occurring due to the adhesion of cells to the
endothelium while passing through the narrow capillary lumen, and the frequency of these stalls
increases with high blood cell counts, enhanced inflammation, enhanced expression of amyloid-
beta (modeling Alzheimer’s disease (AD)) and cerebral ischemia. These stalls are observed to
occur repeatedly in certain capillaries for yet undetermined reasons. Capillary stalls likely
introduce flow heterogeneity and pockets of decreased oxygen tension at a very local level, but
also, cumulatively, they can have global consequences with or without decreasing the cerebral
blood flow. Importantly, our team has shown that pharmacologically reducing the incidence of
these stalls in an AD model immediately resulted in improved cognitive performance. This
clearly indicates the importance of understanding the universal mechanisms and broader
implications of these stalling events that likely result in cognitive decline in a variety of
conditions. Our team has been developing a suite of tools that are uniquely suited to study the
structural and functional heterogeneity of the microvascular network and the impact on tissue
oxygen delivery and function. We are proposing to extend and optimize our techniques to
elucidate the specific causes of capillary stalls in normal physiology, why they repeatedly occur
in certain segments, if they have any role in capillary-level regulation of neurovascular coupling,
and what consequences they have on cerebral metabolism and cell function.

## Key facts

- **NIH application ID:** 10216370
- **Project number:** 5R01NS108472-04
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** David A Boas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $626,919
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216370

## Citation

> US National Institutes of Health, RePORTER application 10216370, The impact of microvascular (dys)regulation on cerebral flow and oxygen heterogeneity (5R01NS108472-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10216370. Licensed CC0.

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