{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T12:50:15Z","timestamp":1760014215045,"version":"3.41.2"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sprague\u2010Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (<jats:italic>n<\/jats:italic>\u00a0=\u00a011). The rats in the EP group received adaptive training for 3 days (10\u00a0m\/min, 20\u00a0min\/day, with a 0\u00b0 incline) and formal training for 3 weeks (6 days\/week, 25\u00a0m\/min, 30\u00a0min\/day, with a 0\u00b0 incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48\u00a0h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre\u2010ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF\u20101 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF\u20101 pathway, which provided novel targets for CIRI treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.3608","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T05:39:02Z","timestamp":1719985142000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["RNA sequencing reveals the potential mechanism of exercise preconditioning for cerebral ischemia reperfusion injury in 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