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Hypothermia-induced coma or death frequently occurs in clinical and forensic settings. Despite this, the precise mechanism of central nervous system injury due to hypothermia remains unclear, hindering the development of targeted clinical treatments and specific forensic diagnostic indicators. The GEO database was searched to identify datasets related to hypothermia. Post-bioinformatics analyses, DEGs, and ferroptosis-related DEGs (FerrDEGs) were intersected. GSEA was then conducted to elucidate the functions of the Ferr-related genes. Animal experiments conducted in this study demonstrated that hypothermia, compared to the control treatment, can induce significant alterations in iron death-related genes such as PPARG, SCD, ADIPOQ, SAT1, EGR1, and HMOX1 in cerebral cortex nerve cells. These changes lead to iron ion accumulation, lipid peroxidation, and marked expression of iron death-related proteins. The application of the iron death inhibitor Ferrostatin-1 (Fer-1) effectively modulates the expression of these genes, reduces lipid peroxidation, and improves the expression of iron death-related proteins. Severe hypothermia disrupts the metabolism of cerebral cortex nerve cells, causing significant alterations in ferroptosis-related genes. These genetic changes promote ferroptosis through multiple pathways.<\/jats:p>","DOI":"10.3390\/ijms25158086","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T06:11:36Z","timestamp":1721887896000},"page":"8086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Severe Hypothermia Induces Ferroptosis in Cerebral Cortical Nerve Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Chao-Long","family":"Lu","sequence":"first","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Jing","family":"Sha","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru-Fei","family":"Ma","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-Tong","family":"Dong","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Rui","family":"Su","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Cong","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song-Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, College of Forensic Medicine, Hebei Medical University, No. 361 Zhong Shan Road, Shijiazhuang 050017, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"k4306","DOI":"10.1136\/bmj.k4306","article-title":"Association between ambient temperature and mortality risk and burden: Time series study in 272 main Chinese cities","volume":"363","author":"Chen","year":"2018","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0140-6736(14)62114-0","article-title":"Mortality risk attributable to high and low ambient temperature: A multicountry observational study","volume":"386","author":"Gasparrini","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. 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