Vagus nerve electrical stimulation in the recovery of upper limb motor functional impairment after ischemic stroke

Ischemic stroke (IS) is characterized by high mortality, disability rates, and a high risk of recurrence. Motor dysfunction, such as limb hemiparesis, dysphagia, auditory disorders, and speech disorders, usually persists after stroke, which imposes a heavy burden on society and the health care system. Traditional rehabilitation therapies may be ineffective in promoting functional recovery after stroke, and alternative strategies are urgently needed. The Food and Drug Administration (FDA) has approved invasive vagus nerve stimulation (iVNS) for the improvement of refractory epilepsy, treatment-resistant depression, obesity, and moderate to severe upper limb motor impairment following chronic ischemic stroke. Additionally, the FDA has approved transcutaneous vagus nerve stimulation (tVNS) for the improvement of cluster headaches and acute migraines. Recent studies have demonstrated that vagus nerve stimulation (VNS) has neuroprotective effects in both transient and permanent cerebral ischemia animal models, significantly improving upper limb motor impairments, auditory deficits, and swallowing difficulties. Firstly, this article reviews two potential neuronal death pathways following IS, including autophagy and inflammatory responses. Then delves into the current status of preclinical and clinical research on the functional recovery following IS with VNS, as well as the potential mechanisms mediating its neuroprotective effects. Finally, the optimal parameters and timing of VNS application are summarized, and the future challenges and directions of VNS in the treatment of IS are discussed. The application of VNS in stroke rehabilitation research has reached a critical stage, and determining how to safely and effectively translate this technology into clinical practice is of utmost importance. Further preclinical and clinical studies are needed to elucidate the therapeutic mechanisms of VNS.