{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:08:23Z","timestamp":1792667303664,"version":"4.5.0"},"reference-count":74,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Purpose<\/jats:bold>\n                    : To synthesize current mechanistic insights and translational progress on ferroptosis, a regulated, iron\u2010dependent, nonapoptotic cell death pathway in the pathophysiology and treatment of cerebral infarction (ischemic stroke), and to outline therapeutic opportunities and remaining gaps for clinical application.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Method<\/jats:bold>\n                    : Narrative, focused review of preclinical and translational studies (in vitro, ex vivo, and in vivo ischemia\/reperfusion and middle cerebral artery occlusion models), alongside emerging biomarker, nanocarrier, and gene\/RNA\u2010based strategies reported up to 2025. Evidence was organized across five domains: (1) redox and lipid peroxidation biology; (2) iron metabolism and ferritinophagy; (3) mitochondrial dysfunction; (4) neuroinflammation and blood\u2013brain barrier integrity; and (5) therapeutic development and early clinical exploration.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Finding<\/jats:bold>\n                    : Ferroptosis in cerebral infarction is driven by glutathione depletion, glutathione peroxidase\u20104 (GPX4) inactivation, and iron\u2010catalyzed lipid peroxidation of polyunsaturated phospholipids, with acyl\u2010CoA synthetase long\u2010chain family member\u20104 (ACSL4) and lysophosphatidylcholine acyltransferase\u20103 (LPCAT3) priming membranes for oxidative injury. Mitochondrial reactive oxygen species, iron\u2013sulfur cluster instability, and cardiolipin oxidation amplify ferroptotic signaling, while ferroptosis\u2013inflammation crosstalk (via damage\u2010associated molecular patterns and microglial activation) aggravates secondary injury and blood\u2013brain barrier disruption. Candidate biomarkers (e.g., oxylipins, 8\u2010iso\u2010prostaglandin F2\u03b1, GPX4 fragments; gene pairs such as CDKN1A\/JUN; NFE2L2 pathway readouts) show promise for patient stratification. Pharmacological approaches\u2014including radical\u2010trapping antioxidants (ferrostatin\u20101, liproxstatin\u20101), iron chelation, and nuclear factor erythroid 2\u2013related factor 2 (Nrf2) activation\u2014consistently reduce infarct volume and improve function in animal models. Nanoparticle formulations enhance brain delivery of ferroptosis modulators, and RNA\/gene\u2010targeted strategies (e.g., SLC7A11\/GPX4\/FSP1 axes; exosomal noncoding RNAs) expand the therapeutic toolkit. Clinically, iron\u2010modulating strategies in ischemic stroke suggest feasibility; however, dedicated, biomarker\u2010guided ferroptosis trials remain limited.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : Ferroptosis represents a convergent, actionable mechanism of ischemic neuronal death and secondary brain injury. Multimodal interventions that combine lipid peroxidation control, iron homeostasis, mitochondrial protection, and inflammation resolution are biologically compelling. Key next steps include: validating real\u2010time biomarkers for patient selection and timing; optimizing brain\u2010penetrant delivery systems; integrating ferroptosis modulation with reperfusion therapies; and advancing rigorously designed phase II\/III trials to establish efficacy and safety in defined stroke subtypes.\n                  <\/jats:p>","DOI":"10.1002\/brb3.71192","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:05:25Z","timestamp":1768547125000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Research Progress of Ferroptosis in Cerebral Infarction"],"prefix":"10.1002","volume":"16","author":[{"given":"Yilan","family":"Fei","sequence":"first","affiliation":[{"name":"Nursing Department, Health Care Center, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou City China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Leng","sequence":"additional","affiliation":[{"name":"Health Care Center, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou City China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118304"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12030501"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/17590914211037505"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14865"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045\u2010024\u201001564\u20103"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00041.2017"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020\u2010024\u201000918\u2010w"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011\u2010022\u201001672\u20101"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2024.13252"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4911205"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010022\u201008295\u20100"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920\u2010025\u201002098\u20104"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118328"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2023.0717"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556\u2010023\u201000142\u20102"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1301822"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2024.2446319"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1528538"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1482386"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010019\u201000710\u2010x"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14604"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/v15122373"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2024.100837"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113611"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41016\u2010024\u201000357\u20104"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207609"},{"key":"e_1_2_12_28_1","doi-asserted-by":"crossref","unstructured":"Lee H. 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