# Cerebral Microvascular Signaling and Neurovascular Coupling: An Integrated Approach to Investigate VCID

> **NIH NIH R01** · FLORIDA INTERNATIONAL UNIVERSITY · 2021 · $540,881

## Abstract

SUMMARY
Neuronal activity leads to increases in local cerebral blood flow (CBF) to allow adequate supply of O2 and
nutrients to active neurons. This process, termed neurovascular coupling (NVC), is essential for survival and its
disruption is associated with cognitive decline and dementia. Despite significant findings, we are still far from
reaching a comprehensive understanding of NVC. This prohibits us from a thorough understanding of normal
brain function and from identifying critical failures in disease and hinders investigations into the vascular origins
of cognitive impairment. The objective of this application is to investigate how K+-mediated local CBF control
emerges from the integration of neuronal inputs and autoregulatory feedback. This will be accomplished by
pursuing two specific aims: In Aim 1, models of endothelial and smooth muscle cells will be developed and
examine K+-mediated electrical signaling in capillaries and arterioles. We propose that the inward rectifying K+
channel acts as bistable, “on-off”, switch to hyperpolarize cell membranes when extracellular K+ increases. Multi-
cellular models of microvascular networks will examine communication between capillaries and their feeding
arteriole, and the significance of capillary-level NVC for local CBF control. We propose that regenerative signal
propagation enables this communication and we will test this hypothesis using modeling and an ex-vivo intact
arteriole-capillary preparation. In Aim 2, simulations in a geometrically accurate vascular network will predict
macroscopic changes in blood flow following functional activation. We will integrate theory and experiments to
analyze channelopathy-like defects, in animal models of cerebral small vessel and Alzheimer's disease. We will
test the hypothesis that impaired capillary-arteriole communication and altered myogenic response lead to a
NVC deficit and propose optimal strategies for restoring this deficit. The proposed work will provide a paradigm
for comprehensive examinations of cerebral blood flow control, for interpreting altered cellular signaling in
disease and for elucidating vascular underpinnings in cognitive impairment.

## Key facts

- **NIH application ID:** 10299245
- **Project number:** 1R01NS119971-01A1
- **Recipient organization:** FLORIDA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** Nikolaos Michael Tsoukias
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $540,881
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10299245

## Citation

> US National Institutes of Health, RePORTER application 10299245, Cerebral Microvascular Signaling and Neurovascular Coupling: An Integrated Approach to Investigate VCID (1R01NS119971-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10299245. Licensed CC0.

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