{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:52:07Z","timestamp":1793130727189,"version":"4.5.0"},"reference-count":76,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"789","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,3,12]]},"abstract":"<jats:p>\n            Traumatic brain injury (TBI) rapidly triggers proinflammatory activation of microglia, contributing to secondary brain damage post-TBI. Although the governing role of energy metabolism in shaping the inflammatory phenotype and function of immune cells has been increasingly recognized, the specific alterations in microglial bioenergetics post-TBI remain poorly understood. Itaconate, a metabolite produced by the enzyme aconitate decarboxylase 1 [IRG1; encoded by immune responsive gene 1 (\n            <jats:italic>Irg1<\/jats:italic>\n            )], is a pivotal metabolic regulator in immune cells, particularly in macrophages. Because microglia are macrophages of the brain parenchyma, the IRG1\/itaconate pathway likely modulates microglial inflammatory responses. In this study, we explored the role of the IRG1\/itaconate pathway in regulating microglial bioenergetics and inflammatory activation post-TBI using a mouse controlled cortical impact (CCI) model. We isolated microglia before and 4 and 12\u00a0hours after TBI and observed a swift but transient increase in glycolysis coupled with a prolonged disruption of mitochondrial metabolism after injury. Despite an up-regulation of Irg1 expression, itaconate in microglia declined after TBI. Microglia-specific\n            <jats:italic>Irg1<\/jats:italic>\n            gene knockout (\n            <jats:italic>Irg1<\/jats:italic>\n            -Mi-KO) exacerbated metabolic changes, intensified proinflammatory activation and neurodegeneration, and worsened certain long-term neurological deficits. Supplementation with 4-octyl itaconate (OI) reinstated the use and oxidative metabolism of glucose, glutamine, and fatty acid, thereby enhancing microglial bioenergetics post-TBI. OI supplementation also attenuated proinflammatory activation and neurodegeneration and improved long-term neurological outcomes. These results suggest that therapeutically targeting the itaconate pathway could improve microglial energy metabolism and neurological outcomes after TBI.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adn2635","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T17:58:22Z","timestamp":1741802302000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":50,"title":["Itaconate restrains acute proinflammatory activation of microglia MG after traumatic brain injury in mice"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-0359","authenticated-orcid":true,"given":"Ning","family":"Liu","sequence":"first","affiliation":[{"name":"Clinical Neuroscience Research Center, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA 70112, USA."},{"name":"Tulane University Translational Sciences Institute, New Orleans, LA 70112, 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