Abstract: Stroke remains a leading cause of death and disability worldwide, and electroacupuncture has a long history of use in stroke treatment. This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke. The PubMed, EMBASE, Web of Science, CENTRAL, and CINAHL databases were comprehensively searched up to May 1, 2024. This review included articles on preclinical investigations of the efficacy and mechanisms of electroacupuncture in treating ischemic stroke. Data from 70 eligible studies were analyzed in Stata 18.0, using a random-effects model to calculate the standardized mean difference (Hedge’s g). The risk of bias was assessed using RevMan 5.4 software, and the quality of evidence was rated according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. Subgroup analyses were conducted to test the consistency of the results and sensitivity analyses were used to assess their robustness. The quality assessment revealed that most studies adequately handled incomplete data and selective reporting. However, several methodological limitations were identified: only 4 studies demonstrated a low risk of allocation concealment, 26 achieved a low risk of outcome assessment bias, and 9 had a high risk of randomization bias. Additionally, there was an unclear risk regarding participant blinding and other methodological aspects. The GRADE assessment rated 12 outcomes as moderate quality and 6 as low quality. The mechanisms of electroacupuncture treatment for ischemic stroke can be categorized as five primary pathways: (1) Electroacupuncture significantly reduced infarct volume and apoptotic cell death (P < 0.01) in ischemic stroke models; (2) electroacupuncture significantly decreased the levels of pro-inflammatory factors (P < 0.01) while increasing the levels of anti-inflammatory factors (P = 0.02); (3) electroacupuncture reduced the levels of oxidative stress indicators (P < 0.01) and enhanced the expression of antioxidant enzymes (P < 0.01); (4) electroacupuncture significantly promoted nerve regeneration (P < 0.01); and (5) electroacupuncture influenced blood flow remodeling (P < 0.01) and angiogenesis (P < 0.01). Subgroup analyses indicated that electroacupuncture was most effective in the transient middle cerebral artery occlusion model (P < 0.01) and in post-middle cerebral artery occlusion intervention (P < 0.01). Dispersive waves were found to outperform continuous waves with respect to neuroprotection and anti-inflammatory effects (P < 0.01), while scalp acupoints demonstrated greater efficacy than body acupoints (P < 0.01). The heterogeneity among the included studies was minimal, and sensitivity analyses indicated stable results. Their methodological quality was generally satisfactory. In conclusion, electroacupuncture is effective in treating cerebral ischemia by modulating cell apoptosis, oxidative stress, inflammation, stroke-induced nerve regeneration, blood flow remodeling, and angiogenesis. The efficacy of electroacupuncture may be influenced by factors such as the middle cerebral artery occlusion model, the timing of intervention onset, waveform, and acupoint selection. Despite the moderate to low quality of evidence, these findings suggest that electroacupuncture has clinical potential for improving outcomes in ischemic stroke.

Key words: apoptosis, angiogenesis, electroacupuncture, ischemic stroke, inflammation, metaanalysis, nerve regeneration, oxidative stress, randomized controlled trial, systematic review