• Beibei Yu, Yongfeng Zhang, Yunze Tian, and Shouping Gong.
• Department of Neurourgery, Second Affiliated Hospital of Xi'an Jiao Tong University, Shaanxi Province, China.
• World Neurosurg. 2022 Dec 1; 168: 278286.e2278-286.e2.

BackgroundCell-derived exosomes bearing microRNAs (miRNAs) have emerged as a potential therapeutic option for cerebral ischemia-reperfusion injury (CIRI). However, their mechanism of action and clinical translation value remain unclear. The present meta-analysis investigated the therapeutic effects of miRNA-modified exosomes used in preclinical animal models of CIRI.MethodsThe PubMed, Embase, and Web of Science databases were searched on April 20, 2022, to retrieve studies involving middle cerebral artery occlusion model animals treated with exosomes bearing miRNAs. The primary outcome was infarct volume, and the secondary outcome was neurobehavioral performance. FunRich software was used for bioinformatic analysis of exosomal miRNAs, and statistical analysis was performed using R version 4.1.1 (R Foundation for Statistical Computing).ResultsEleven relevant studies were included in the meta-analysis. miRNA-modified exosomes significantly reduced infarct volume (standardized mean difference [SMD], 4.50 [95% confidence interval, 3.02-5.99]; P < 0.01) and improved neurological score (SMD, 2.80 [95% confidence interval, 1.37-4.23]; P < 0.01). Subgroup analysis revealed that a higher injection frequency of exosomes could better reduce infarct volume. The top 6 biological pathways, expression sites, and transcription factors of related exosomal miRNAs were identified through bioinformatics analysis. An asymmetrical funnel plot and Egger's test (P = 0.10) revealed publication bias. Trim-and-fill analysis identified 5 unpublished studies addressing the primary outcome.ConclusionsmiRNA-modified exosomal therapy demonstrated the potential to improve infarct volume and neurobehavioral performance in preclinical animal models of CIRI. Despite the heterogeneity among studies, the results may provide some direction for future clinical research.Copyright © 2022 Elsevier Inc. All rights reserved.

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