Non-invasive Vagus Nerve Stimulation in Cerebral Stroke: Current Status and Future Perspectives

Abstract

Stroke poses a serious threat to human health and burdens both society and the healthcare system. Standard rehabilitative therapies may not be effective in improving functions after stroke, so alternative strategies are needed. The FDA has approved vagus nerve stimulation (VNS) for the treatment of epilepsy, migraines, and depression. Recent studies have demonstrated that VNS can facilitate the benefits of rehabilitation interventions. VNS coupled with upper limb rehabilitation enhances the recovery of upper limb function in patients with chronic stroke. However, its invasive nature limits its clinical application. Researchers have developed a non-invasive method to stimulate the vagus nerve (non-invasive vagus nerve stimulation, nVNS). It has been suggested that nVNS coupled with rehabilitation could be a promising alternative for improving muscle function in chronic stroke patients. In this article, we review the current researches in preclinical and clinical studies as well as the potential applications of nVNS in stroke. We summarize the parameters, advantages, potential mechanisms, and adverse effects of current nVNS applications, as well as the future challenges and directions for nVNS in cerebral stroke treatment. These studies indicate that nVNS has promising efficacy in reducing stroke volume and attenuating neurological deficits in ischemic stroke models. While more basic and clinical research is required to fully understand its mechanisms of efficacy, especially Phase III trials with a large number of patients, these data suggest that nVNS can be applied easily not only as a possible secondary prophylactic treatment in chronic cerebral stroke, but also as a promising adjunctive treatment in acute cerebral stroke in the near future.

Efficacy and Safety of Vagus Nerve Stimulation on Upper Limb Motor Recovery After Stroke. A Systematic Review and Meta-Analysis

“…The magnitude of reduction in infarct size has been similar to the one reported for implanted VNS (18). In addition to these effects, transcutaneous VNS has shown to regulate other mechanisms that can promote recovery of neurological function after ischemic stroke (38,39). These include upregulation of angiogenesis, which can improve perfusion of the tissue surrounding the injury promoting recovery (40), regulation of blood brain barrier permeability, which could improve cerebral edema after stroke (41), and inhibition of neuroinflammation resulting in neuroprotective effects against ischemic cerebral injuries (37).…”

Motor and Cognitive Modulation of a Single Session of Transcutaneous Auricular Vagus Nerve Stimulation in Post Stroke Patients: A Pilot Study

“…The release of neurotransmitters enhances the synaptic plasticity and the reorganization of cortical networks which ultimately improves motor function [33]. Considering the sensorimotor system, there is a growing number of studies reporting behavioral and electrophysiological effects of tVNS on motor functions [34], [35]. Changes in corticospinal excitability using a paired-pulse TMS protocol were found with a significant increase of short-interval intracortical inhibition in the right motor cortex following 1-hour of tVNS application [36].…”

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients

“…An inverted U-shaped relationship between the degree of cortical plasticity induced by tVNS and its frequency has been found, with vagal stimulation at moderate frequencies (30 Hz) enhancing cortical plasticity, whereas neither slower (7.5 Hz) nor faster (120 Hz) pulse frequencies significantly enhance plasticity [ 102 ]. Therefore, tVNS with frequencies of 20 Hz, 25 Hz, and 30 Hz are commonly used in clinical trials for post-stroke rehabilitation [ 19 , 103 ]. In addition, the enhancement of cortical plasticity and memory due to vagal stimulation is also influenced by pulse width.…”