# Non-invasive vagus nerve stimulation to mitigate subarachnoid hemorrhage induced inflammation

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $194,375

## Abstract

Project Summary/Abstract. Between 3-5% of adults harbor an intracranial aneurysm1, and subarachnoid
hemorrhages (SAH) resulting from ruptured aneurysms are associated with a mortality rate of 10-25% with an
additional 30% of patients suffering permanent disability2. Inflammation plays a central role, driving the morbidity
associated with SAH. Despite understanding the important role of inflammation in morbidity following SAH, the
current barrier is that there is no effective methodology to modulate the deleterious inflammatory response in
patients following SAH. Due to this gap, there is a critical need for a novel approach to immunomodulation that
can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a novel,
non-pharmacologic approach to immunomodulation. Studies have demonstrated VNS to reduce systemic
inflammatory markers3 and VNS has had early success treating inflammatory conditions such as arthritis4,
sepsis5, and inflammatory bowel diseases6,7. Our long-term goal is to translate the use of non-invasive
transcutaneous auricular VNS (taVNS) to reduce morbidity and improve outcomes in patients following
spontaneous SAH. The overall objectives for this application in pursuit of achieving this goal are to (i)
demonstrate the impact taVNS has on a key inflammatory marker in the blood and CSF in patients following
SAH, and (ii) determine if taVNS reduces the incidence of inflammation-mediated sequelae of SAH by performing
a prospective, randomized controlled trial. Our central hypothesis is that implementing taVNS in the acute period
following spontaneous SAH will attenuate the expected inflammatory response to hemorrhage and will curtail
morbidity associated with inflammatory-mediated clinical endpoints (i.e., vasospasm, hydrocephalus). Our
hypothesis has been formulated based on preliminary findings where our team applied taVNS in a cohort of SAH
patients leading to reductions in white blood cell count, TNF- α, and IL-6 in the CSF, as well as early evidence
of decreased vasospasm and chronic hydrocephalus. Guided by this preliminary data, we will test our central
hypothesis with the following specific aims: 1) Define the impact that transcutaneous auricular vagus nerve
stimulation has on a key subarachnoid hemorrhage-induced inflammatory marker, TNF-α, in the serum and
cerebrospinal fluid (CSF), 2) Determine that taVNS following SAH reduces angiographic vasospasm, and 3)
Determine that taVNS following SAH reduces chronic hydrocephalus. We will perform a randomized controlled
study on aneurysmal SAH patients where we will test whether twice daily treatment with taVNS compared to
sham will alter these physiologic and clinical endpoints. This project is innovative because it diverges from the
pharmacologic status quo by harnessing a novel non-invasive neuromodulatory approach and its known anti-
inflammatory effects to alter the pathophysiology of SAH. The development of a new and effective inter...

## Key facts

- **NIH application ID:** 10870057
- **Project number:** 5R21NS128307-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Peter Brunner
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,375
- **Award type:** 5
- **Project period:** 2023-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870057

## Citation

> US National Institutes of Health, RePORTER application 10870057, Non-invasive vagus nerve stimulation to mitigate subarachnoid hemorrhage induced inflammation (5R21NS128307-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10870057. Licensed CC0.

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