# Analysis of the Outcomes Studied in the Application of Invasive and Non-Invasive Vagus Nerve Stimulation in Clinical and Preclinical Studies Involving Stroke—A Scoping Review

## TL;DR

This review summarizes outcomes of vagus nerve stimulation studies for stroke treatment, highlighting a need for more clinical research.

## Contribution

The study provides a comprehensive overview of outcomes studied in VNS for stroke, identifying gaps in clinical research.

## Key findings

- Forty-one experimental and sixteen clinical studies on VNS for stroke were analyzed.
- Outcomes included neuroprotection, rehabilitation, and dysphagia, with limited clinical effectiveness data.
- Preclinical studies focused on molecular mechanisms, while clinical studies remain scarce.

## Abstract

Background: Currently, there is a considerable number of studies addressing vagus nerve stimulation (VNS) for the treatment of different stroke-related outcomes. We aimed to promote a broad view of the outcomes studied and what are the opportune outcomes to be studied involving this therapeutic strategy for the treatment of post-stroke complications. Methods: This is a scoping review that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two investigators conducted independent searches on PubMed/MEDLINE, Scopus, and Embase till July 2025. Randomized clinical trials and preclinical studies using invasive or non-invasive vagus nerve stimulation conducted with a population diagnosed with stroke were included. Results: Forty-one experimental studies and sixteen clinical trials were included. The outcomes found were neuroprotection; motor, functional, and cognitive rehabilitation; dysphagia; comparison of different stimulation intensities; safety, efficacy, and feasibility of the non-invasive approach; comparison between transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS); and comparison between two models of ischemia (permanent and transient). Preclinical studies mostly investigated molecular elements involved in neuroprotection, neuroinflammation, and cellular apoptosis, while clinical studies evaluating the effectiveness of this technique used for rehabilitation and its comparison or combination with other techniques remain scarce. Conclusions: Most studies investigating the effects of VNS on different post-stroke outcomes are experimental studies. Clinical studies are still scarce and with limited analysis of outcomes.