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This study investigated contributions of circRNAs to PE\u2010induced improvements in post\u2010stroke neurological function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats subjected to transient middle cerebral artery occlusion were left sedentary or provided running\u2010wheel access for 4\u2009weeks during recovery. CircRNAs from peri\u2010infarct cortex were identified by high\u2010throughput sequencing, and interactions with miRNAs by immunoprecipitation, fluorescence in suit hybridization, and dual\u2010luciferase reporter assays. In\u00a0vivo circRNA knockdown was achieved using shRNA\u2010AAVs and in\u00a0vitro overexpression by plasmid transfection. Transmission electron microscopy, western blotting, and TUNEL assays were conducted to explore circRNA contributions to endoplasmic reticulum (ER) stress and neuronal apoptosis. CircRNA levels were measured in plasma from stroke patients by qRT\u2010PCR and associations with neurological scores assessed by Pearson's correlation analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PE upregulated circAnks1b, reduced infarct volume, and mitigated neurological dysfunction, while circAnks1b knockdown exacerbated neurological dysfunction and increased infarct size despite PE. CircAnks1b sponged miR\u2010130b\u20105p, thereby disinhibiting Pak2 expression. Conversely, Pak2 downregulation disrupted PE\u2010mediated protective ER stress, leading to reduced IRE1\/XBP1 and heightened apoptosis. Plasma circAnks1b was higher in stroke patients receiving PE than sedentary patients and correlated negatively with neurological scores.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CircAnks1b upregulation may be an effective therapeutic strategy for post\u2010stroke recovery.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70055","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T08:22:24Z","timestamp":1727425344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Physical exercise\u2010induced <scp>circAnks1b<\/scp> upregulation promotes protective endoplasmic reticulum stress and suppresses apoptosis via <scp>miR<\/scp>\u2010130b\u20105p\/Pak2 signaling in an ischemic stroke 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