# Evaluation of the Neuromodulatory Mechanisms of Vagus Nerve Stimulation to Improve Motor Rehabilitation after Stroke

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2020 · $334,688

## Abstract

PROJECT ABSTRACT
Stroke is a leading cause of disability, with an estimated 795,000 cases in the US each year. As many as 70%
of patients who suffer a stroke exhibit long-term impairment in upper extremity motor function. The
development of rehabilitative strategies to improve the recovery of motor function is of key importance.
Neuroplasticity is believed to support recovery after stroke; therefore, manipulations that enhance plasticity
may increase recovery. Stimulation of the vagus nerve during motor training drives robust, specific
neuroplasticity in rat motor cortex. Recent evidence indicates that vagus nerve stimulation (VNS) delivered
during rehabilitative training significantly improves recovery of forelimb function in multiple models of stroke,
but the mechanisms underlying VNS-dependent enhancement of recovery are not defined. The cholinergic and
noradrenergic neuromodulatory systems are engaged by VNS and represent potential pathways through which
VNS may support recovery. We propose to delineate the neuromodulatory pathways and mechanisms by
which VNS acts to increase recovery of forelimb motor function after stroke. The first aim of the study will
determine whether the cholinergic and noradrenergic systems are required for VNS-dependent enhancement
of recovery after stroke. The second aim of the study will evaluate whether direct stimulation of the cholinergic
or noradrenergic systems during rehabilitative training is sufficient to enhance recovery. The third aim of the
proposal will examine whether anatomical reorganization in descending motor networks is enhanced by VNS
therapy to support functional recovery.
The results of the proposed experiments will delineate the neuromodulatory pathways and mechanisms by
which VNS paired with rehabilitative training enhances recovery after stroke. Insights from these studies will
help to determine whether common disease-related and pharmacological factors that influence these
neuromodulatory systems may interfere with the beneficial effects of VNS. Ultimately, results from this study
will improve the likelihood of successful translation of VNS therapy for stroke patients.

## Key facts

- **NIH application ID:** 9973199
- **Project number:** 5R01NS094384-05
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** SETH ALANSON HAYS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,688
- **Award type:** 5
- **Project period:** 2016-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973199

## Citation

> US National Institutes of Health, RePORTER application 9973199, Evaluation of the Neuromodulatory Mechanisms of Vagus Nerve Stimulation to Improve Motor Rehabilitation after Stroke (5R01NS094384-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9973199. Licensed CC0.

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