Invasive or non-invasive vagus nerve stimulation modulation of brain function and remodeling after stroke: a review

Background: The main reason restricting stroke patients from reintegrating into society is neurological deficits. Of particular interest is the potential vagus nerve stimulation (VNS) potentially offers for sustaining improvement in neurological deficits. The goal of the present study is to provide a summary of the findings from research that has been carried out to elucidate the mechanisms and demonstrate the efficacy and safety of the clinical application of VNS, as well as to identify research gaps in the field, in order to offer references for subsequent further research and application. Methods: A systematic search was conducted in the PubMed, Web of Science, Embase, and Ovid MEDLINE databases (1866 publications). An initial screening of abstracts and titles was performed, followed by a thorough review and assessment of the full texts of 253 relevant papers. Results: Ultimately, 62 studies that met the eligibility criteria were included. VNS may be performed either invasively or non-invasively. The modulation of brain function that is produced by VNS may improve cerebral function by one or more of the following means, namely stimulating the pathway that regulates synaptic plasticity, inhibiting inflammatory response, promoting vascular regeneration or protecting the blood–brain barrier. Application of invasive VNS has produced promising results in the treatment of moderate/severe upper limb dyskinesia in patients with ischemic stroke and has gradually entered clinical practice. Furthermore, transcutaneous auricular VNS has also demonstrated potential therapeutic effects (standardized mean differences 1.16, 95% CI = 0.02–2.30). However, further developments are required in many aspects, including preventing indications of dysfunction, optimization of parameters, timing and duration of stimulation and site of application. Conclusions: The VNS as a promising therapeutic approach for stroke rehabilitation. The application of VNS in the treatment of hemorrhagic stroke is still unexplored and warrants attention in future studies.