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However, despite an expanding body of literature, knowledge of ferroptosis has not yet translated into meaningful advances for neurological conditions in humans. Here, we summarize evidence supporting the hypothesis that intracerebral hemorrhage, as a prototypical iron-overload disorder, induces tissue damage and functional impairment through ferroptotic mechanisms. Specifically, erythrocyte lysis releases hemoglobin and its degradation product hemin, promoting lipid peroxidation and antioxidant collapse, culminating in neuronal ferroptosis. We further propose that endogenous homeostatic responses driven by pharmacological selenium supplementation, including a novel selenium-based peptide developed in our laboratory, represent effective strategies to mitigate injury and improve functional recovery in rodent models of hemorrhagic and ischemic stroke. Given reproducible effects across models and laboratories, we argue that anti-ferroptotic interventions, particularly those that limit the toxic effects of redox-active iron and reinforce GPX4-centered defenses, warrant advancement toward human clinical trials.<\/jats:p>","DOI":"10.1177\/0271678x261421833","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:07:29Z","timestamp":1771243649000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Ironing out mechanisms of ferroptotic death to tailor new stroke therapies"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2723-5355","authenticated-orcid":false,"given":"Geena FM","family":"Capps","sequence":"first","affiliation":[{"name":"Medical Sciences Division, University of Oxford, Oxford, UK"},{"name":"Burke Neurological Institute, Weill Cornell Medicine, White Plains, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6403-1808","authenticated-orcid":false,"given":"Anna CJ","family":"Kalisvaart","sequence":"additional","affiliation":[{"name":"Burke Neurological Institute, Weill Cornell Medicine, White Plains, NY, USA"},{"name":"Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9081-2701","authenticated-orcid":false,"given":"Rajiv R","family":"Ratan","sequence":"additional","affiliation":[{"name":"Burke Neurological Institute, Weill Cornell Medicine, White Plains, NY, USA"},{"name":"Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/17474930241307876"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16405-2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000407"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2308440"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fstro.2023.1155937"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01323"},{"key":"e_1_3_3_8_2","first-page":"24","article-title":"Modes of brain cell death following intracerebral hemorrhage","volume":"16","author":"\u200cZhang Y","year":"2022","unstructured":"\u200cZhang Y, Khan S, Liu Y, et al. 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