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Circular RNAs (circRNAs) are highly abundant in the brain, and exert regulatory roles during post-transcriptional process. Recently, deregulations of circRNA expression have been proven to be involved in hypoxia cells in vitro. However, the circRNA profiles of penumbra closely related to the prognosis of acute ischemic stroke (AIS) remain unclear. Herein, 12876 circRNAs based on circBase database were detected by microarray hybridization with blood RNA samples of Balb/c mice, including the sham group and groups of 5 min, 3 hr and 24 hr after middle cerebral artery occlusion (MCAO). Three comparison groups were set as sham vs 5 min (311 circRNAs up-regulated, 566 circRNAs down-regulated), sham vs 3 hr (513 circRNAs up-regulated, 207 circRNAs down-regulated), sham vs 24 hr (1079 circRNAs up-regulated, 1230 circRNAs down-regulated) (≥2.0 fold, p<0.05). Meanwhile, using RNA-sequencing technology, we profiled circRNA expressional signatures of mice brain tissues from normal zones, penumbra and infract zones of MCAO 3 hr groups. 553 of the total 23980 circRNAs changed significantly between the differential expression profiles of penumbra vs normal and penumbra vs infract core. Among them, two circRNAs sequence were aligned with the blood data by Pairwise Sequence Alighment (SIMILARITY=100%, IDENTITY=100%). Moreover, human-mouse alignments of the two circRNAs were computed on circBase database (IDENTITY >94.8% and IDENTITY=100%). Bioinformatics tools and databases were employed to explore the potential circRNAs functions. These findings are the first to identify MCAO-responsive circRNAs, which suggest potential pathological roles and may be as potential markers for penumbra progress in AIS.