Understanding the Neuroplastic Effects of Auricular Vagus Nerve Stimulation in Animal Models of Stroke: A Systematic Review and Meta-Analysis
Paulo S. de Melo, J.M. Parente, Ingrid Rebello‐Sanchez, Anna Marduy, Anna Carolyna Gianlorenço, Chi Kyung Kim, Sung‐Hyuk Choi, Jae‐Jun Song, Felipe Fregni
Abstract
Background Transauricular vagus nerve stimulation (taVNS) is being studied as a feasible intervention for stroke, but the mechanisms by which this non-invasive technique acts in the cortex are still broadly unknown. Objectives This study aimed to systematically review the current pre-clinical evidence in the auricular vagus nerve stimulation (aVNS) neuroplastic effects in stroke. Methods We searched, in December of 2022, in Medline, Cochrane, Embase, and Lilacs databases. The authors executed the extraction of the data on Excel. The risk of bias was evaluated by adapted Cochrane Collaboration’s tool for animal studies (SYRCLES’s RoB tool). Results A total of 8 studies published between 2015 and 2022 were included in this review, including 391 animal models. In general, aVNS demonstrated a reduction in neurological deficits (SMD = −1.97, 95% CI −2.57 to −1.36, I 2 = 44%), in time to perform the adhesive removal test (SMD = −2.26, 95% CI −4.45 to −0.08, I 2 = 81%), and infarct size (SMD = −1.51, 95% CI −2.42 to −0.60, I 2 = 58%). Regarding the neuroplasticity markers, aVNS showed to increase microcapillary density, CD31 proliferation, and BDNF protein levels and RNA expression. Conclusions The studies analyzed show a trend of results that demonstrate a significant effect of the auricular vagal nerve stimulation in stroke animal models. Although the aggregated results show high heterogeneity and high risk of bias. More studies are needed to create solid conclusions.