Noninvasive or minimally invasive neuromodulation in animal models of acute ischemic stroke: A systematic review and meta‐analysis

Abstract

Abstract Background Neuromodulation therapy has emerged as a potential brain cytoprotective strategy in the hyperacute phase of ischemic stroke (IS). This systematic review aimed to evaluate the cytoprotective effects of neuromodulation in animal models of IS. Methods A systematic search of the MEDLINE, Embase, and LILACS databases was conducted to identify in vivo preclinical studies that investigated noninvasive or minimally invasive neuromodulation therapy administered within 24 h of arterial occlusion and included a control group. The primary outcome was infarct volume, and the secondary outcomes included assessments of neurological function using validated behavioral scales. Random‐effects meta‐analyses were performed for all outcomes using the Cochrane Review Manager software (version 5.4.1). The protocol was prospectively registered in the International Prospective Register of Systematic Reviews database (No. CRD42020165347). Results Thirty studies were included in the qualitative synthesis (2347 reported animals), and 25 studies were eligible for meta‐analysis. Most studies employed middle cerebral artery occlusion models. Neuromodulation techniques included electroacupuncture, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and vagus nerve stimulation. Pooled analyses demonstrated that neuromodulation significantly reduced infarct volume both in absolute (standardized mean difference [SMD]: −0.80; p < 0.001) and relative terms (SMD: −2.01; p < 0.001) and improved neurological outcomes (SMD: −1.53; p = 0.006). However, considerable heterogeneity was observed across studies and interventions. Conclusion Neuromodulation confers brain cytoprotective effects in experimental IS models; however, the high heterogeneity in stimulation parameters and outcomes limits its translational potential. Standardization of experimental protocols and reporting is required to improve reproducibility.