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

Figure 2. Forest plot: the outcome of vagus nerve stimulation (VNS) on neurological deficit score. The effect of each study (“favors control”, “favors treatment”, or “no effect”) was estimated through the standardized mean difference (horizontal axis). The dashed vertical line at 0 indicates that the study was determined to have “no effect”. The horizontal bars in each chart plot represent the mean difference with a 95% confidence interval for each study [21,22,23,24,25,26,27,28,29,30,31,32,35,38,39,40,41,42,49].

Figure 3. Forest plot: the outcome of vagus nerve stimulation (VNS) on infarct size reported as percentage reduction (%). The effect of each study (“favors control”, “favors treatment”, or “no effect”) was estimated through the standardized mean difference (horizontal axis). The dashed vertical line at 0 indicates that the study was determined to have “no effect”. The horizontal bars in each chart plot represent the mean difference with a 95% confidence interval for each study [22,23,26,32,34,35,37,38,39,41,42,49].

Figure 4. Forest plot: the outcome of vagus nerve stimulation (VNS) on infarct volume reported in mm3. The effect of each study (“favors control”, “favors treatment”, or “no effect”) was estimated through the standardized mean difference (horizontal axis). The dashed vertical line at 0 indicates that the study was determined to have “no effect”. The horizontal bars in each chart plot represent the mean difference with a 95% confidence interval for each study [21,24,25,26,31,34,40].

Figure 5. Forest plot: the outcome of vagus nerve stimulation (VNS) on forelimb strength. The effect of each study (“favors Rehab”, “favors VNS & Rehab”, or “no effect”) was estimated through the standardized mean difference (horizontal axis). The dashed vertical line at 0 indicates that the study was determined to have “no effect”. The horizontal bars in each chart plot represent the mean difference with a 95% confidence interval for each study [43,44,45,46,47,48].

Figure 6. The average forelimb strength in the Rehab group (solid fill) and VNS along with Rehab group (pattern fill) over 5 weeks post stroke injury. The forelimb strength between groups were significantly different on the 5th weeks of VNS treatment and rehab n = 5. *** p < 0.001 [43,44,45,46,47].

Figure 1. The systematic review process. The flow diagram outlines the search and selection process that was applied in the systematic review of published studies. All review steps were based on the PRISMA guidelines. Records (n) relate to the number of database searches, the number of abstracts screened, and the number of full texts obtained.

Figure 7. Vagus nerve stimulation has shown to improve stroke with various proposed mechanisms such as anti-apoptosis, angiogenesis and anti-inflammation. NTS—Nucleus of the solitary tract, a7nAChR—a7-nicotinic acetylcholine receptor, BDNF—Brain Derived Neurotrophic Factor, VEGF—Vascular endothelial growth factor, p-Akt—phosphorylated protein kinase B.