The Effects of Vagus Nerve Stimulation on Animal Models of Stroke-Induced Injury: A Systematic Review

SIMPLE SUMMARY: Ischemic stroke is one of the most common causes of death worldwide, putting a significant strain on society and the healthcare system. In recent years, significant progress has been made in the treatment of ischemic stroke. However, owing to the ever-increasing cost of medical care, there is an urgent need to develop alternative treatments for stroke prevention and treatment. Vagus nerve stimulation, currently approved for the treatment of depression and epilepsy, has emerged as a useful therapeutic approach in recent decades. Although numerous animal studies have been conducted on vagus nerve stimulation, particularly in stroke conditions, little effort has been made to examine them together. In this review, we compiled and compared the findings of VNS studies up to June 2022. Vagus nerve stimulation was found to improve most of the stroke parameters examined. We concluded that, specifically in an animal model, vagus nerve stimulation may be a treatment option that helps alleviate stroke symptoms. These findings may be beneficial for future translational research in animal models and patients with stroke. ABSTRACT: Ischemic stroke is one of the leading causes of death worldwide, and poses a great burden to society and the healthcare system. There have been many recent advances in the treatment of ischemic stroke, which usually results from the interruption of blood flow to a particular part of the brain. Current treatments for ischemic stroke mainly focus on revascularization or reperfusion of cerebral blood flow to the infarcted tissue. Nevertheless, reperfusion injury may exacerbate ischemic injury in patients with stroke. In recent decades, vagus nerve stimulation (VNS) has emerged as an optimistic therapeutic intervention. Accumulating evidence has demonstrated that VNS is a promising treatment for ischemic stroke in various rat models through improved neural function, cognition, and neuronal deficit scores. We thoroughly examined previous evidence from stroke-induced animal studies using VNS as an intervention until June 2022. We concluded that VNS yields stroke treatment potential by improving neurological deficit score, infarct volume, forelimb strength, inflammation, apoptosis, and angiogenesis. This review also discusses potential molecular mechanisms underlying VNS-mediated neuroprotection. This review could help researchers conduct additional translational research on patients with stroke.