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In the United States, the health burden of TBI is compounded by the high incidence of alcohol involvement, with up to 50% of cases occurring in intoxicated individuals and approximately 26% of patients consuming alcohol post\u2010injury. This review synthesizes current research exploring the complex interplay between TBI and alcohol misuse, with a particular focus on their combined effects on mitochondrial function, energy metabolism, and cellular redox homeostasis. We discuss how TBI\u2010induced mitochondrial dysfunction, manifested as impaired adenosine triphosphate (ATP) production, excessive reactive oxygen species (ROS) generation, and subsequent depletion of glutathione, intersects with alcohol\u2010mediated metabolic reprogramming, resulting in disrupted glucose metabolism and a shift toward glutaminolysis. This metabolic perturbation predisposes neural tissue to lipid peroxidation and ferroptosis, an iron\u2010dependent form of cell death that is characterized by the peroxidation of polyunsaturated fatty acid\u2010containing phospholipids. Here we highlight how alterations in glutamate homeostasis in combination with exacerbated neuroinflammatory signaling contribute to post\u2010TBI cognitive impairments and hinder the recovery process. Integrating findings from biomarker studies and preclinical models, we highlight the critical need for targeted therapies that address these interconnected molecular pathways. A comprehensive understanding of these pathways promises to uncover druggable targets leading to novel neuroprotective strategies, offering hope for improved clinical outcomes in patients suffering from TBI, particularly those with concurrent alcohol exposure.<\/jats:p>","DOI":"10.1111\/acer.70267","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:16:37Z","timestamp":1773004597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Traumatic brain injury and alcohol: A narrative review of the role of mitochondrial dysfunction and ferroptosis in neurocognitive outcomes"],"prefix":"10.1111","volume":"50","author":[{"given":"Xavier R.","family":"Chapa\u2010Dubocq","sequence":"first","affiliation":[{"name":"Louisiana State University, Health Sciences Center Department of Physiology  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Vita","sequence":"additional","affiliation":[{"name":"Louisiana State University, Health Sciences Center Department of Physiology  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Guzm\u00e1n\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Neural Sciences Alzheimer's Center, Lewis Katz School of Medicine, Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3598-384X","authenticated-orcid":false,"given":"Patricia E.","family":"Molina","sequence":"additional","affiliation":[{"name":"Louisiana State University, Health Sciences Center Department of Physiology  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010021\u201000616\u20103"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.21315\/mjms2024.31.3.4"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1374735"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26083531"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2023.0502"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.04.038"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2024.07.003"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.9.2.271"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975\u2010011\u20100123\u2010z"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010025\u201002360\u20105"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010021\u201001266\u20101"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph182412925"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306285200"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010022\u201001185\u20103"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00156\u201016"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2009.09.003"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9020169"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/16501960410023859"},{"key":"e_1_2_12_20_1","unstructured":"CDC. 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