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MicroRNAs (miRNAs) are involved in cerebral ischemia\/reperfusion (I\/R) injury, but their involvement in CXCR7\u2010mediated brain protection is unknown. In this study, we investigated the role of miRNAs in CXCR7\u2010mediated brain protection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CXCR7 levels in peripheral blood samples from patients with acute ischemic stroke (AIS) and ischemic penumbra area brain tissues from middle cerebral artery occlusion (MCAO) rats after recanalization were measured. An miRNA microarray analysis was performed to examine the expression of miRNAs caused by CXCR7 knockdown in ischemic penumbra area brain tissue in middle cerebral artery occlusion\u2013reperfusion rats and to predict corresponding downstream target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed the most enriched pathways. A dual\u2010luciferase reporter assay confirmed the direct regulation of miR\u2010182 on the target gene TCF7L2. The correlation between TCF7L2 and CXCR7\/miR\u2010182 was verified using rescue assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CXCR7 expression was upregulated in MCAO rats and mechanical thrombectomy patients with AIS compared to that in controls. The motor and sensory functions of MCAO rats with CXCR7 knockdown further decreased, and the infarct volume and cerebral edema increased. miRNA microarray data showed that seven miRNAs were differentially expressed after shRNA\u2010CXCR7 treatment. The dual\u2010luciferase reporter assay confirmed that miR\u2010182 directly targeted the TCF7L2 gene. Rescue assays confirmed that TCF7L2 is downstream of CXCR7\/miR\u2010182. KEGG pathway analysis showed that the Hippo pathway may be a key pathway in CXCR7 upregulation and plays a role in protecting the brain after interventional surgery. Animal experiments have shown that CXCR7\u2010mediated cerebral I\/R injury promotes the phosphorylation of key molecules YAP and TAZ in the Hippo pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CXCR7 protects against cerebral I\/R injury, possibly via the miR\u2010182\/TCF7L2\/Hippo pathway. These results indicate that CXCR7 affects cerebral ischemia\u2013reperfusion injury through miRNA regulation and downstream pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14056","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T06:36:06Z","timestamp":1671172566000},"page":"712-726","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Chemokine receptor 7 mediates <scp>miRNA<\/scp>\u2010182 to regulate cerebral ischemia\/reperfusion injury in rats"],"prefix":"10.1111","volume":"29","author":[{"given":"Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Wannan Medical College Yijishan Hospital  Wuhu China"},{"name":"Key Laboratory of Noncoding RNA Transformation Research of Anhui Higher Education Institutes Wannan Medical College  Wuhu 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