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Iranian Journal of Basic Medical Sciences، جلد ۲۸، شماره ۱۲، صفحات ۱۶۹۹-۱۷۰۵
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عنوان انگلیسی Temporal dynamics of ferroptosis markers and neuroprotective intervention in cerebral ischemia-reperfusion injury: Insights for therapeutic strategy development
چکیده انگلیسی مقاله Objective(s): This study examines the temporal dynamics of ferroptosis following cerebral ischemia-reperfusion injury (CIRI) to establish a theoretical framework for innovative therapies that enhance neuronal survival by mitigating ferroptosis.Materials and Methods: An experimental CIRI model was established in mice via middle cerebral artery occlusion and reperfusion (MCAO/R). Behavioral assessments were conducted, and blood-brain barrier (BBB) integrity was evaluated using transmission electron microscopy. Immunoblotting and ELISA were performed to determine ferroptosis dynamics post-MCAO/R. Additionally, CIRI mice received intraperitoneal injections of Ferrostain-1 (10 mg/kg/d) and Erastin (30 mg/kg/d). The effects of ferroptosis on CIRI were further verified through 2,3,5-Triphenyltetrazolium chloride and hematoxylin-eosin staining.Results: MCAO/R induced BBB disruption, and was associated with a reduction in GSH activity (at 1, 3, and 5 days), elevated Fe(2+) levels (at 1 day), as well as decreased MDA levels (at 3 days). Concurrently, ferroptosis markers, including NRF2, xCT, and GPX4, were significantly down-regulated on day 1, reaching their nadir by day 3, whereas HO-1 exhibited an inverse trend. Notably, Ferrostatin-1 pretreatment conferred a protective effect against CIRI, in contrast to the MCAO and Erastin groups.Conclusion: This study elucidates the temporal dynamics of ferroptosis markers in the early stages of stroke, highlighting a therapeutic window for ferroptosis-related CIRI. These findings underscore the importance of targeting ferroptosis to improve neuronal survival and inform future CIRI therapies.
کلیدواژه‌های انگلیسی مقاله Blood-brain barrier, Ferroptosis, Ischemic stroke, Lipid Peroxidation, Oxidative stress
نویسندگان مقاله | Shuangyan Bao
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China|National-Local Joint Engineering Research Center of Entomoceutics, Dali, PR China


| Chaojie Liu
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China|National-Local Joint Engineering Research Center of Entomoceutics, Dali, PR China


| Qian Wang
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China|National-Local Joint Engineering Research Center of Entomoceutics, Dali, PR China


| Chenggui Zhang
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China|National-Local Joint Engineering Research Center of Entomoceutics, Dali, PR China


| Hairong Zhao
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, Yunnan, PR China|National-Local Joint Engineering Research Center of Entomoceutics, Dali, PR China
نشانی اینترنتی https://ijbms.mums.ac.ir/article_26673.html
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