# Vascular Signaling Plasticity - Novel Concepts and Tools for Studying Neurovascular Interactions in Health and Disease

> **NIH NIH DP2** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $2,317,500

## Abstract

SUMMARY
The brain requires a vast amount of energy (around 20% of the total generated in the body) to function normally.
Despite this, the brain lacks energy stores and instead uses a ‘just-in-time’ energy delivery system known as
‘functional hyperemia’, in which local blood flow increases in response to spikes in neuronal activity. This process
is underlain by a range of redundant ‘neurovascular coupling’ mechanisms that collectively ensure the fidelity of
the blood flow response to feed activity. We have discovered that these mechanisms display a striking form of
plasticity, in which chronic changes in neuronal energy requirements lead to reprogramming of these vascular
signaling mechanisms to augment or dampen the local delivery of blood. We term this phenomenon vascular
signaling plasticity (VSP). Importantly, VSP is disrupted in a mouse model of Alzheimer’s disease, implying that
loss of this process may lead to a mismatch between energy supply and demand and impair neuronal function.
Here, we propose a program of research in which we develop novel workflows for chronic imaging of VSP in
awake behaving animals, followed by detailed molecular analyses of the mechanisms that underlie VSP in the
same cells that we image. This work will reveal a previously unknown and unsuspected mechanism for blood
flow control in the brain that is critical for neuronal health, opening a new field of research into the phenomenon
of VSP. Completion of this project will deliver a range of imaging tools to enable us to image blood flow and
aspects of VSP non-invasively over long periods in vivo, and our work will culminate in the development of a
novel brain endothelium-specific gene therapy aimed at protecting or restoring VSP in dementia, thereby
safeguarding neuronal metabolism and function.

## Key facts

- **NIH application ID:** 10002378
- **Project number:** 1DP2NS121347-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Thomas A Longden
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,317,500
- **Award type:** 1
- **Project period:** 2020-08-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10002378

## Citation

> US National Institutes of Health, RePORTER application 10002378, Vascular Signaling Plasticity - Novel Concepts and Tools for Studying Neurovascular Interactions in Health and Disease (1DP2NS121347-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10002378. Licensed CC0.

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