# Targeted neuromodulation to enhance recovery of the aged brain after ischemic stroke

> **NIH NIH R21** · DUKE UNIVERSITY · 2022 · $442,750

## Abstract

Abstract
Ischemic stroke, a devasting disease that primarily affects the elderly, is a leading cause of long-term disability
worldwide. Current treatment relies primarily on restoring blood flow during the acute phase after stroke.
However, this reperfusion treatment is applicable to only a small fraction of stroke patients, and even among
these patients, many still suffer life-long neurologic impairment. Thus, there is an urgent need for new recovery-
enhancing treatments during the chronic stroke phase. In the chronic phase after stroke, spontaneous, but
typically slow and partial, recovery of neurologic function occurs due to activation of endogenous restorative
processes not only in the peri-infarct region but also in remote brain regions. These processes involve neuronal
plasticity. To enhance neuronal plasticity, neuromodulation strategies, including brain stimulation, have been
explored in neurorehabilitation stroke therapy. However, the clinical results have been inconsistent, highlighting
a deficiency in our knowledge about the role of specific neuronal activity in neurorestoration after stroke. Our
long-term goal is to help design effective neuromodulatory stroke therapy that enhances recovery, particularly in
the aged brain. Our objective here is to combine novel and state-of-the-art approaches to clarify the role of
neuronal activity in the chronic stroke recovery phase, through a detailed dissection of mechanisms at cellular
and network levels in aged mice of both sexes. In particular, we will capitalize on the power of Designer
Receptors Exclusively Activated by Designer Drugs (DREADDs)-based chemogenetics to modulate specific
neurons in the post-stroke brain. Our central hypothesis is that after ischemic stroke, proper modulation of
targeted neuronal activity during the chronic recovery phase promotes vascularization, corticospinal tract (CST)
reorganization, interhemispheric connectivity, and restoration of brain function. To test this hypothesis, we will
pursue 2 specific aims: 1) Modulate excitatory neurons in peri-infarct regions during chronic stroke recovery
phase; and 2) Modulate excitatory neurons in the contralateral M1 region during chronic stroke recovery phase.
The proposed research is significant because knowledge we will gain from this study is expected to inform future
development of novel interventions that promote recovery of brain function after ischemic stroke through targeted
neuromodulation, thus improving quality of life in stroke patients.

## Key facts

- **NIH application ID:** 10593316
- **Project number:** 1R21NS127163-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Wei Yang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $442,750
- **Award type:** 1
- **Project period:** 2022-09-21 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10593316

## Citation

> US National Institutes of Health, RePORTER application 10593316, Targeted neuromodulation to enhance recovery of the aged brain after ischemic stroke (1R21NS127163-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10593316. Licensed CC0.

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