{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:46:50Z","timestamp":1792104410822,"version":"4.4.0"},"reference-count":161,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Taiwan","award":["R113-021"],"award-info":[{"award-number":["R113-021"]}]},{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["CGH-MR-A11425"],"award-info":[{"award-number":["CGH-MR-A11425"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Oxidative stress is a defining feature of stroke pathology, but the magnitude, timing and impact of redox imbalance are not static. Emerging evidence indicates that physiological contexts, such as aging, metabolic stress, and circadian disruption, continuously reshape oxidative status and determine the brain\u2019s vulnerability to ischemic and reperfusion injury. This review integrates recent insights into how these intrinsic modulators govern the transition from adaptive physiological redox signaling to pathological oxidative stress during stroke. Aging compromises mitochondrial quality control and blunts NRF2-driven antioxidant responses, heightening susceptibility to ROS-driven damage. Metabolic dysfunction, as seen in obesity and diabetes, amplifies oxidative burden through NADPH oxidase activation, lipid peroxidation, and impaired glutathione recycling, further aggravating post-ischemic inflammation. Circadian misalignment, meanwhile, disrupts the rhythmic expression of antioxidant enzymes and metabolic regulators such as BMAL1, REV-ERB\u03b1, and SIRT1, constricting the brain\u2019s temporal window of resilience. We highlight convergent signaling hubs, NRF2\/KEAP1, SIRT\u2013PGC1\u03b1, and AMPK pathways, as integrators of these physiological inputs that collectively calibrate redox homeostasis. Recognizing oxidative stress as a dynamic, context-dependent process reframes it from a static pathological state to a dynamic outcome of systemic and temporal imbalance, offering new opportunities for time-sensitive and metabolism-informed redox interventions in stroke.<\/jats:p>","DOI":"10.3390\/antiox15010054","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:34:23Z","timestamp":1767198863000},"page":"54","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dynamic Oxidative States: Interplay of Aging, Metabolic Stress, and Circadian Rhythms in Modulating Stroke Severity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4878-5084","authenticated-orcid":false,"given":"Jui-Ming","family":"Sun","sequence":"first","affiliation":[{"name":"Section of Neurosurgery, Department of Surgery, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chia-Yi 600, Taiwan"},{"name":"Department of Nursing, School of Nursing, Fooyin University, Kaohsiung 831, Taiwan"},{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0524-113X","authenticated-orcid":false,"given":"Jing-Shiun","family":"Jan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Ta","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery, Cathay General Hospital, Taipei 106, Taiwan"},{"name":"School of Medicine, National Tsing Hua University, Hsinchu 300, Taiwan"},{"name":"Department of Medicine, School of Medicine, Fu Jen Catholic University, New Taipei 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2147-2990","authenticated-orcid":false,"given":"Rajeev","family":"Taliyan","sequence":"additional","affiliation":[{"name":"Neuropsychopharmacology Division, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Pilani Campus, Pilani 333031, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8354-7874","authenticated-orcid":false,"given":"Chih-Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Research Center for Neuroscience, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruei-Dun","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Medical Research, Taipei Medical University Hospital, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-0521","authenticated-orcid":false,"given":"Ting-Lin","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Medical Research, Cathay General Hospital, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wu, L., Xiong, X., Wu, X., Ye, Y., Jian, Z., Zhi, Z., and Gu, L. 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