{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:00:40Z","timestamp":1787162440094,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T00:00:00Z","timestamp":1702252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82071328"],"award-info":[{"award-number":["82071328"]}]},{"name":"National Natural Science Foundation of China","award":["SBK2019022915"],"award-info":[{"award-number":["SBK2019022915"]}]},{"name":"National Natural Science Foundation of China","award":["22LCYY-QH11"],"award-info":[{"award-number":["22LCYY-QH11"]}]},{"name":"National Natural Science Foundation of China","award":["YYBJ2021041"],"award-info":[{"award-number":["YYBJ2021041"]}]},{"name":"Jiangsu Natural Science Foundation of China","award":["82071328"],"award-info":[{"award-number":["82071328"]}]},{"name":"Jiangsu Natural Science Foundation of China","award":["SBK2019022915"],"award-info":[{"award-number":["SBK2019022915"]}]},{"name":"Jiangsu Natural Science Foundation of China","award":["22LCYY-QH11"],"award-info":[{"award-number":["22LCYY-QH11"]}]},{"name":"Jiangsu Natural Science Foundation of China","award":["YYBJ2021041"],"award-info":[{"award-number":["YYBJ2021041"]}]},{"name":"Jinling Hospital","award":["82071328"],"award-info":[{"award-number":["82071328"]}]},{"name":"Jinling Hospital","award":["SBK2019022915"],"award-info":[{"award-number":["SBK2019022915"]}]},{"name":"Jinling Hospital","award":["22LCYY-QH11"],"award-info":[{"award-number":["22LCYY-QH11"]}]},{"name":"Jinling Hospital","award":["YYBJ2021041"],"award-info":[{"award-number":["YYBJ2021041"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The occurrence of early brain injury (EBI) significantly contributes to the unfavorable prognosis observed in patients with subarachnoid hemorrhage (SAH). During the process of EBI, a substantial quantity of iron permeates into the subarachnoid space and brain tissue, thereby raising concerns regarding its metabolism. To investigate the role and metabolic processes of excessive iron in neurons, we established both in vivo and in vitro models of SAH. We substantiated that ferritinophagy participates in iron metabolism disorders and promotes neuronal ferroptosis using an in vivo model, as detected by key proteins such as ferritin heavy chain 1, glutathione peroxidase 4, autophagy related 5, nuclear receptor coactivator 4 (NCOA4), LC3B, and electron microscopy results. By interfering with NCOA4 expression in vitro and in vivo, we confirmed the pivotal role of elevated NCOA4 levels in ferritinophagy during EBI. Additionally, our in vitro experiments demonstrated that the addition of oxyhemoglobin alone did not result in a significant upregulation of NCOA4 expression. However, simultaneous addition of oxyhemoglobin and hypoxia exposure provoked a marked increase in NCOA4 expression and heightened ferritinophagy in HT22 cells. Using YC-1 to inhibit hypoxia signaling in in vitro and in vitro models effectively attenuated neuronal ferroptosis. Collectively, we found that the hypoxic microenvironment during the process of EBI exaggerates iron metabolism abnormalities, leading to poor prognoses in SAH. The findings also offer a novel and potentially effective foundation for the treatment of SAH, with the aim of alleviating hypoxia.<\/jats:p>","DOI":"10.3390\/antiox12122097","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T06:56:00Z","timestamp":1702277760000},"page":"2097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hypoxia Aggravates Neuron Ferroptosis in Early Brain Injury Following Subarachnoid Hemorrhage via NCOA4-Meditated Ferritinophagy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2059-1680","authenticated-orcid":false,"given":"Zixuan","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingtao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China"},{"name":"Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6822-3268","authenticated-orcid":false,"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China"},{"name":"Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/S0140-6736(22)00938-2","article-title":"Spontaneous Subarachnoid Haemorrhage","volume":"400","author":"Claassen","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1161\/STROKEAHA.122.040072","article-title":"Early Brain Injury After Subarachnoid Hemorrhage: Incidence and Mechanisms","volume":"54","author":"Lauzier","year":"2023","journal-title":"Stroke"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chen, Y., Galea, I., Macdonald, R.L., Wong, G.K.C., and Zhang, J.H. (2022). Rethinking the Initial Changes in Subarachnoid Haemorrhage: Focusing on Real-Time Metabolism during Early Brain Injury. EBioMedicine, 83.","DOI":"10.1016\/j.ebiom.2022.104223"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s11910-021-01136-9","article-title":"Aneurysmal Subarachnoid Hemorrhage: Review of the Pathophysiology and Management Strategies","volume":"21","author":"Osgood","year":"2021","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/ana.26083","article-title":"Superficial Siderosis: A Clinical Review","volume":"89","author":"Kumar","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1161\/STROKEAHA.121.037670","article-title":"Are We Looking Into an Iron Age for Subarachnoid Hemorrhage?","volume":"53","author":"Plesnila","year":"2022","journal-title":"Stroke"},{"key":"ref_7","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. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1080344","DOI":"10.3389\/fncel.2023.1080344","article-title":"Ferroptosis: Underlying Mechanism and the Crosstalk with Other Modes of Neuronal Death after Intracerebral Hemorrhage","volume":"17","author":"Cao","year":"2023","journal-title":"Front. Cell. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114171","DOI":"10.1016\/j.expneurol.2022.114171","article-title":"S100A8 Regulates Autophagy-Dependent Ferroptosis in Microglia after Experimental Subarachnoid Hemorrhage","volume":"357","author":"Tao","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ren, S., Chen, Y., Wang, L., and Wu, G. (2022). Neuronal Ferroptosis after Intracerebral Hemorrhage. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.966478"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/s41419-023-05978-8","article-title":"Autophagy Mediates an Amplification Loop during Ferroptosis","volume":"14","author":"Lee","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1080\/15548627.2016.1187366","article-title":"Autophagy Promotes Ferroptosis by Degradation of Ferritin","volume":"12","author":"Hou","year":"2016","journal-title":"Autophagy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3389\/fnins.2019.00238","article-title":"NCOA4-Mediated Ferritinophagy: A Potential Link to Neurodegeneration","volume":"13","author":"Mancias","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Santana-Codina, N., and Mancias, J.D. (2018). The Role of NCOA4-Mediated Ferritinophagy in Health and Disease. Pharmaceuticals, 11.","DOI":"10.20944\/preprints201809.0148.v1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature13148","article-title":"Quantitative Proteomics Identifies NCOA4 as the Cargo Receptor Mediating Ferritinophagy","volume":"509","author":"Mancias","year":"2014","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7794","DOI":"10.1080\/21655979.2021.1975999","article-title":"Baicalin Suppresses Autophagy-Dependent Ferroptosis in Early Brain Injury after Subarachnoid Hemorrhage","volume":"12","author":"Zheng","year":"2021","journal-title":"Bioengineered"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1177\/0271678X15608389","article-title":"Cerebral Microcirculatory Failure after Subarachnoid Hemorrhage Is Reversed by Hyaluronidase","volume":"36","author":"McConnell","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1097\/00000542-200002000-00026","article-title":"Hypoxic Brain Tissue Following Subarachnoid Hemorrhage","volume":"92","author":"Hoffman","year":"2000","journal-title":"Anesthesiology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/acn3.170","article-title":"HIF-1\u03b1 Mediates Isoflurane-Induced Vascular Protection in Subarachnoid Hemorrhage","volume":"2","author":"Milner","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1038\/jcbfm.2013.173","article-title":"The Role of the Microcirculation in Delayed Cerebral Ischemia and Chronic Degenerative Changes after Subarachnoid Hemorrhage","volume":"33","author":"Aamand","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e021113","DOI":"10.1161\/JAHA.121.021113","article-title":"Sirtuin 1 Mediates Protection Against Delayed Cerebral Ischemia in Subarachnoid Hemorrhage in Response to Hypoxic Postconditioning","volume":"10","author":"Diwan","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113484","DOI":"10.1016\/j.expneurol.2020.113484","article-title":"SIRT1 Mediates Hypoxic Preconditioning Induced Attenuation of Neurovascular Dysfunction Following Subarachnoid Hemorrhage","volume":"334","author":"Vellimana","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13054-015-0809-9","article-title":"Early Brain Injury after Aneurysmal Subarachnoid Hemorrhage: A Multimodal Neuromonitoring Study","volume":"19","author":"Helbok","year":"2015","journal-title":"Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1161\/STROKEAHA.123.043976","article-title":"Nimodipine Reduces Microvasospasms After Experimental Subarachnoid Hemorrhage","volume":"54","author":"Schwarting","year":"2023","journal-title":"Stroke"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1111\/cns.13222","article-title":"Clinical and Experimental Aspects of Aneurysmal Subarachnoid Hemorrhage","volume":"25","author":"Daou","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"522","DOI":"10.7150\/thno.49426","article-title":"Melanocortin 1 Receptor Attenuates Early Brain Injury Following Subarachnoid Hemorrhage by Controlling Mitochondrial Metabolism via AMPK\/SIRT1\/PGC-1\u03b1 Pathway in Rats","volume":"11","author":"Xu","year":"2021","journal-title":"Theranostics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1080\/14756366.2020.1758691","article-title":"Biochemical Mechanism and Biological Effects of the Inhibition of Silent Information Regulator 1 (SIRT1) by EX-527 (SEN0014196 or Selisistat)","volume":"35","author":"Broussy","year":"2020","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1007\/s12035-016-9776-7","article-title":"Melatonin Attenuates Early Brain Injury via the Melatonin Receptor\/Sirt1\/NF-\u03baB Signaling Pathway Following Subarachnoid Hemorrhage in Mice","volume":"54","author":"Zhao","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.freeradbiomed.2018.06.035","article-title":"Cerebroprotection by Salvianolic Acid B after Experimental Subarachnoid Hemorrhage Occurs via Nrf2- and SIRT1-Dependent Pathways","volume":"124","author":"Zhang","year":"2018","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118050","DOI":"10.1016\/j.lfs.2020.118050","article-title":"Neuroprotective Role of Glutathione Peroxidase 4 in Experimental Subarachnoid Hemorrhage Models","volume":"257","author":"Gao","year":"2020","journal-title":"Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41420-021-00656-0","article-title":"Inhibition of DNMT-1 Alleviates Ferroptosis through NCOA4 Mediated Ferritinophagy during Diabetes Myocardial Ischemia\/Reperfusion Injury","volume":"7","author":"Li","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41419-020-2248-z","article-title":"Inhibition of AIM2 Inflammasome Activation Alleviates GSDMD-Induced Pyroptosis in Early Brain Injury after Subarachnoid Haemorrhage","volume":"11","author":"Yuan","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hao, G., Eser, P., and Mo, J. (2022). Oxidative Stress and Intracranial Hypertension after Aneurysmal Subarachnoid Hemorrhage. Antioxidants, 11.","DOI":"10.3390\/antiox11122423"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Huang, Y., Wu, H., Hu, Y., Zhou, C., Wu, J., Wu, Y., Wang, H., Lenahan, C., Huang, L., and Nie, S. (2022). Puerarin Attenuates Oxidative Stress and Ferroptosis via AMPK\/PGC1\u03b1\/Nrf2 Pathway after Subarachnoid Hemorrhage in Rats. Antioxidants, 11.","DOI":"10.3390\/antiox11071259"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1027756","DOI":"10.3389\/fimmu.2022.1027756","article-title":"Inflammation and Immune Cell Abnormalities in Intracranial Aneurysm Subarachnoid Hemorrhage (SAH): Relevant Signaling Pathways and Therapeutic Strategies","volume":"13","author":"Jin","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1136\/jnnp-2021-326920","article-title":"Age and Outcome after Aneurysmal Subarachnoid Haemorrhage","volume":"92","author":"Macdonald","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"153113","DOI":"10.1016\/j.tox.2022.153113","article-title":"ROS and Iron Homeostasis Dependent Ferroptosis Play a Vital Role in 5-Fluorouracil Induced Cardiotoxicity in Vitro and in Vivo","volume":"468","author":"Li","year":"2022","journal-title":"Toxicology"},{"key":"ref_38","first-page":"244","article-title":"The Mechanism and Relevant Mediators Associated with Neuronal Apoptosis and Potential Therapeutic Targets in Subarachnoid Hemorrhage","volume":"18","author":"Tian","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ijsu.2020.07.009","article-title":"Impact of Hyperglycemia on Neuronal Apoptosis after Subarachnoid Hemorrhage in Rodent Brain: An Experimental Research","volume":"83","author":"Huang","year":"2020","journal-title":"Int. J. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1025708","DOI":"10.3389\/fncel.2022.1025708","article-title":"Molecular Mechanisms of Neuronal Death in Brain Injury after Subarachnoid Hemorrhage","volume":"16","author":"Chen","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref_41","first-page":"2691","article-title":"NCOA4 Is Regulated by HIF and Mediates Mobilization of Murine Hepatic Iron Stores after Blood Loss","volume":"136","author":"Li","year":"2020","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105933","DOI":"10.1016\/j.phrs.2021.105933","article-title":"Nuclear Receptor Coactivator 4-Mediated Ferritinophagy Contributes to Cerebral Ischemia-Induced Ferroptosis in Ischemic Stroke","volume":"174","author":"Li","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/s41388-020-01622-3","article-title":"Loss of COPZ1 Induces NCOA4 Mediated Autophagy and Ferroptosis in Glioblastoma Cell Lines","volume":"40","author":"Zhang","year":"2021","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"930958","DOI":"10.3389\/fphar.2022.930958","article-title":"Caryophyllene Oxide Induces Ferritinophagy by Regulating the NCOA4\/FTH1\/LC3 Pathway in Hepatocellular Carcinoma","volume":"13","author":"Xiu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Li, K., Chen, B., Xu, A., Shen, J., Li, K., Hao, K., Hao, R., Yang, W., Jiang, W., and Zheng, Y. (2022). TRIM7 Modulates NCOA4-Mediated Ferritinophagy and Ferroptosis in Glioblastoma Cells. Redox Biol., 56.","DOI":"10.1016\/j.redox.2022.102451"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1007\/s11064-021-03477-w","article-title":"Ferritinophagy Is Involved in Experimental Subarachnoid Hemorrhage-Induced Neuronal Ferroptosis","volume":"47","author":"Liang","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e13107","DOI":"10.1111\/cpr.13107","article-title":"Curcumol Inhibits Ferritinophagy to Restrain Hepatocyte Senescence through YAP\/NCOA4 in Non-Alcoholic Fatty Liver Disease","volume":"54","author":"Qi","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112114","DOI":"10.1016\/j.fct.2021.112114","article-title":"Arsenite Induces Ferroptosis in the Neuronal Cells via Activation of Ferritinophagy","volume":"151","author":"Xiao","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1080\/15548627.2023.2170960","article-title":"ATM Orchestrates Ferritinophagy and Ferroptosis by Phosphorylating NCOA4","volume":"19","author":"Wu","year":"2023","journal-title":"Autophagy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1097\/WNR.0000000000001835","article-title":"Activation of HIF-1\u03b1\/VEGF-A Pathway by Deferoxamine Ameliorates Retinal Hypoxia in a Rat Subarachnoid Hemorrhage Model","volume":"33","author":"Deji","year":"2022","journal-title":"Neuroreport"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sun, X.-G., Chu, X.-H., Godje Godje, I.S., Liu, S.-Y., Hu, H.-Y., Zhang, Y.-B., Zhu, L.-J., Wang, H., Sui, C., and Huang, J. (2022). Aerobic Glycolysis Induced by mTOR\/HIF-1\u03b1 Promotes Early Brain Injury After Subarachnoid Hemorrhage via Activating M1 Microglia. Transl. Stroke Res.","DOI":"10.1007\/s12975-022-01105-5"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1182\/blood.2021013452","article-title":"Modulation of the HIF2\u03b1-NCOA4 Axis in Enterocytes Attenuates Iron Loading in a Mouse Model of Hemochromatosis","volume":"139","author":"Das","year":"2022","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Weiland, J., Beez, A., Westermaier, T., Kunze, E., Sir\u00e9n, A.-L., and Lilla, N. (2021). Neuroprotective Strategies in Aneurysmal Subarachnoid Hemorrhage (aSAH). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115442"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.4103\/1673-5374.339000","article-title":"Obstructive Sleep Apnea Aggravates Neuroinflammation and Pyroptosis in Early Brain Injury Following Subarachnoid Hemorrhage via ASC\/HIF-1\u03b1 Pathway","volume":"17","author":"Xu","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhang, F., Lin, B., Huang, S., Wu, P., Zhou, M., Zhao, J., Hei, X., Ke, Y., Zhang, Y., and Huang, D. (2023). Melatonin Alleviates Retinal Ischemia\u2013Reperfusion Injury by Inhibiting P53\u2013Mediated Ferroptosis. Antioxidants, 12.","DOI":"10.3390\/antiox12061173"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"230182","DOI":"10.1155\/2015\/230182","article-title":"Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms","volume":"2015","author":"Gammella","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101470","DOI":"10.1016\/j.molmet.2022.101470","article-title":"Ferroptosis and Ferritinophagy in Diabetes Complications","volume":"60","author":"He","year":"2022","journal-title":"Mol. Metab."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/12\/2097\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:36:31Z","timestamp":1760132191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/12\/2097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,11]]},"references-count":57,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["antiox12122097"],"URL":"https:\/\/doi.org\/10.3390\/antiox12122097","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,11]]}}}