Understanding the Neuroplastic Effects of Auricular Vagus Nerve Stimulation in Animal Models of Stroke: A Systematic Review and Meta-Analysis

Paulo S. de Melo, João Parente, Ingrid Rebello-Sanchez, Anna Marduy, Anna Carolyna Gianlorenco, Chi Kyung Kim, Hyuk Choi, Jae-Jun Song, Felipe Fregni

Research output: Contribution to journalReview articlepeer-review

1 Citation (Scopus)


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, I2 = 44%), in time to perform the adhesive removal test (SMD = −2.26, 95% CI −4.45 to −0.08, I2 = 81%), and infarct size (SMD = −1.51, 95% CI −2.42 to −0.60, I2 = 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.

Original languageEnglish
Pages (from-to)564-576
Number of pages13
JournalNeurorehabilitation and Neural Repair
Issue number8
Publication statusPublished - 2023 Aug

Bibliographical note

Publisher Copyright:
© The Author(s) 2023.


  • animal models
  • auricular vagal nerve stimulation
  • meta-analysis
  • stroke
  • systematic review

ASJC Scopus subject areas

  • Rehabilitation
  • Neurology
  • Clinical Neurology


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