{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:39:56Z","timestamp":1791484796524,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2308200"],"award-info":[{"award-number":["2023YFC2308200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Cerebral ischemia\u2013reperfusion (I\/R) injury is a critical pathological process in stroke, characterized by disrupted energy metabolism, inflammatory responses, and mitochondrial dysfunction. Targeting mitochondrial dynamics presents promising strategies for alleviating brain injury. This study investigates the role and mechanism of Gastrodin (Gas) in regulating mitochondrial dynamics and mitigating cerebral I\/R injury via activation of the AMPK\u2010OPA1 signaling pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>An in\u00a0vitro oxygen\u2013glucose deprivation\/reperfusion (OGD\/R) model and an in\u00a0vivo middle cerebral artery occlusion\/reperfusion (MCAO\/R) model were used to assess the effects of Gas on inflammation, mitochondrial function, and energy metabolism. Immunofluorescence, western blotting (WB), reverse\u2010transcription PCR (RT\u2010PCR), JC\u20101 staining, and molecular docking techniques were employed for analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gas activated the AMPK\u2010OPA1 signaling pathway, promoting mitochondrial fusion, restoring membrane potential, enhancing ATP production, and rebalancing NAD<jats:sup>+<\/jats:sup>\/NADH levels. Additionally, Gas significantly suppressed I\/R\u2010induced inflammatory responses, reduced neuronal damage, and decreased infarct volume. Notably, its protective effects on mitochondrial fusion and neuroprotection were abolished under AMPK silencing, highlighting the critical role of the AMPK\u2010OPA1 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Gas alleviates cerebral I\/R injury by regulating mitochondrial dynamics via the AMPK\u2010OPA1 signaling pathway. These findings provide a theoretical basis for the therapeutic application of Gas in stroke and offer new insights into mitochondrial\u2010targeted treatment strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70559","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T06:37:11Z","timestamp":1754980631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gastrodin Attenuates Cerebral Ischemia\u2013Reperfusion Injury by Enhancing Mitochondrial Fusion and Activating the <scp>AMPK<\/scp>\u2010<scp>OPA1<\/scp> Signaling Pathway"],"prefix":"10.1111","volume":"31","author":[{"given":"Zihan","family":"Liu","sequence":"first","affiliation":[{"name":"Jiangsu Province Engineering Research Center of Classical Prescription, School of Pharmacy Nanjing University of Chinese Medicine  Nanjing 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