{
  "abstract": "Traumatic brain injury (TBI) is a leading cause of mortality and long-term disability, yet effective pharmacological therapies remain unavailable. Early blood–brain barrier (BBB) disruption accelerates neuroinflammation and secondary brain injury. It has been well recognized that brain microvascular endothelial cells (BMECs) depend on mitochondrial oxidative metabolism to maintain BBB integrity. Here, we investigated the role of the mitochondria-derived immunometabolite itaconate in regulating cerebrovascular bioenergetics and BBB integrity after TBI. Using a controlled cortical impact model, we found that TBI induced early Irg1 upregulation but paradoxically reduced fatty acid–derived itaconate levels in brain microvessels (MVs). TBI also created a hypoxic microenvironment that disrupted the Irg1/itaconate axis in BMECs. Genetic Irg1 deficiency exacerbated microvascular metabolic dysfunction, particularly deficits in fatty acid oxidation (FAO), and BBB breakdown, whereas treatment with 4-octyl itaconate (4-OI) restored mitochondrial metabolism/bioenergetics in brain MVs within 12 h after injury and preserved BBB integrity. Mechanistically, TBI and hypoxia suppressed carnitine palmitoyltransferase 1A (CPT1a), whereas 4-OI restored CPT1a expression, enhanced FAO, and activated Nrf2 signaling, thereby preserving tight junction proteins and VE-cadherin in hypoxia-exposed human BMECs. Together, these findings identify itaconate as a critical regulator of endothelial mitochondrial metabolism and BBB integrity following TBI and support therapeutic targeting of the Irg1/itaconate pathway to prevent secondary neurovascular injury.",
  "abstract_shown": true,
  "affiliations": [
    "Clinical Neuroscience Research Center, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA, 70112, USA; Department of Neurosurgery, School of Medicine, University of Virginia, Charlottesville, VA, 22903, USA",
    "Clinical Neuroscience Research Center, Department of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA, 70112, USA",
    "Harvard Center for Mass Spectrometry, Harvard University, Cambridge, MA, 02138, USA",
    "Tulane University Translational Sciences Institute, New Orleans, LA, 70112, USA",
    "Center for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, LA, USA; Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA, 70112, USA",
    "Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, 70112, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "Ning Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Di Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengxuan Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuwen Xiu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yinghua Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yingjie Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Gaby A. Moyano"
    },
    {
      "affs": [
        1
      ],
      "name": "Jack L. McGuire"
    },
    {
      "affs": [
        1
      ],
      "name": "Amin Iskender"
    },
    {
      "affs": [
        1
      ],
      "name": "Mitchell D. Kilgore"
    },
    {
      "affs": [
        0
      ],
      "name": "Lixiang Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Charles Vidoudez"
    },
    {
      "affs": [
        3
      ],
      "name": "Yadan Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Thin Yadanar Sein"
    },
    {
      "affs": [
        4
      ],
      "name": "Jia Fan"
    },
    {
      "affs": [
        5
      ],
      "name": "Prasad V.G. Katakam"
    },
    {
      "affs": [
        0
      ],
      "name": "Aaron S. Dumont"
    },
    {
      "name": "Xiaoying Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eb1e0n668326d.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104446",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2213231726004453",
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  "landing_url": "https://doi.org/10.1016/j.redox.2026.104446",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
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    ],
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      "lcc",
      "QH301-705.5"
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      "2808|Barrier Structure and Function Studies"
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  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718853/pdf/?tool=EBI",
  "pmcid": "PMC13718853",
  "pmid": "42914897",
  "published": "2026-10-20",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/eb1e0n668326d.ris",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Barrier Structure and Function Studies",
      "subfield": "neurology"
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  ],
  "title": "Itaconate protects the blood-brain barrier by preserving microvascular bioenergetics after traumatic brain injury",
  "title_text": "Itaconate protects the blood-brain barrier by preserving microvascular bioenergetics after traumatic brain injury",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:48Z",
  "url": "https://research.draconitic.com/paper/eb1e0n668326d",
  "venue": "Redox Biology",
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}