{
  "abstract": "While moderate-to-severe traumatic brain injury (msTBI) frequently occurs alongside extracranial injury, the pathophysiology of polytrauma remains incompletely understood. Aeromedical evacuation (AE) from remote settings may introduce additional physiological stress. The kynurenine pathway (KP) is of interest due to its involvement in inflammation, excitotoxicity, oxidative stress, and energy metabolism. This study used a porcine model to examine serum KP metabolite concentrations following closed-head rotational msTBI with 40% hemorrhagic shock (TBI + HS) and the effects of AE. Yucatan minipigs (n = 24) were randomized to Mock flight (stationary at ground level at 5400 ft), standard (∼8500 ft), or tactical evacuation (∼500 ft above ground level) using a U.S. Army Black Hawk helicopter. Blood samples were collected at baseline, 35, 105, and 210 min, and 24 h post-injury. Serum kynurenic acid (KYNA), quinolinic acid (QUIN), and 3-Hydroxykynurenine (3-HK) concentrations were quantified. A separate sham cohort (n = 10) was analyzed at baseline, 35 min, and 24 h. For TBI + HS, microglial activation was inferred from ionized calcium-binding adaptor molecule 1 (Iba1) immunohistochemistry in post-mortem brain tissue at 24 h. Results showed markedly increased KYNA, QUIN and KYNA/QUIN ratio following TBI + HS, peaking at 35 min post-injury and returning to baseline or below by 24 h. 3-HK was elevated at baseline and showed only a modest increase at 210 min. Robust increases in KP metabolite concentrations were observed at 35 min relative to sham. Both AE conditions were associated with lower 24-h KYNA compared with Mock flight. No differences in microglial activation, as assessed by Iba1 staining, were observed between AE groups. However, within the TBI + HS cohort, strong negative correlations were observed between KYNA and KYNA/QUIN (at 35-210 min) and microglial activation. KYNA and the KYNA/QUIN ratio were positively associated with lactate, glial fibrillary acidic protein, and ubiquitin carboxy-terminal hydrolase L1. These findings indicate robust KP activation following TBI + HS, likely caused by the acute release of catecholamines and inflammatory markers, with minimal effects of AE. The mechanistic role of the KP in polytrauma needs to be further assessed in clinical populations to evaluate its potential for targeted modulation, for example focused on an immunomodulatory role for KYNA.",
  "abstract_shown": true,
  "affiliations": [
    "Neurology Department, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.",
    "The Mind Research Network/Lovelace Biomedical Research Institute, Pete & Nancy Domenici Hall, 1101 Yale Blvd. NE, Albuquerque, NM, 87106, USA.",
    "Department of Neuroscience, University of New Mexico School of Medicine, Albuquerque, NM, 8713, USA.",
    "Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA.",
    "Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.",
    "Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI, USA.",
    "Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, 171 77, Sweden.",
    "U.S. Army Aeromedical Research Laboratory, Fort Rucker, AL, USA.",
    "Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.",
    "Boston Children's Hospital, Boston, MA, 02115, USA.",
    "Neurology Department, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA.",
    "Psychiatry Department, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA.",
    "Psychology Department, University of New Mexico, Albuquerque, NM, 87131, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Harm J van der Horn"
    },
    {
      "affs": [
        2
      ],
      "name": "Kristin E Connors"
    },
    {
      "affs": [
        2
      ],
      "name": "Carissa J Mehos Milliken"
    },
    {
      "affs": [
        1
      ],
      "name": "Upasana Nathaniel"
    },
    {
      "affs": [
        0
      ],
      "name": "Koen Visser"
    },
    {
      "affs": [
        1
      ],
      "name": "Tracey V Wick"
    },
    {
      "affs": [
        1
      ],
      "name": "Samuel D Miller"
    },
    {
      "affs": [
        1
      ],
      "name": "Andrew P Gigliotti"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Timothy B Meier"
    },
    {
      "affs": [
        6
      ],
      "name": "Sophie Erhardt"
    },
    {
      "affs": [
        7
      ],
      "name": "Rachel Kinsler"
    },
    {
      "affs": [
        8
      ],
      "name": "Claude van der Ley"
    },
    {
      "affs": [
        8
      ],
      "name": "Martijn van Faassen"
    },
    {
      "affs": [
        8
      ],
      "name": "Ido P Kema"
    },
    {
      "affs": [
        0
      ],
      "name": "Joukje van der Naalt"
    },
    {
      "affs": [
        9
      ],
      "name": "Rebekah Mannix"
    },
    {
      "affs": [
        1,
        10,
        11,
        12
      ],
      "name": "Andrew R Mayer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1hpgynvhs3vv8.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bbih.2026.101389",
  "fulltext_url": "https://europepmc.org/articles/PMC13694781",
  "id": "1hpgynvhs3vv8",
  "issns": [
    "2666-3546"
  ],
  "landing_url": "https://europepmc.org/article/MED/42927136",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Traumatic Brain Injury and Neurovascular Disturbances"
    ]
  ],
  "openalex": "W7221728948",
  "pdf_url": "https://europepmc.org/articles/PMC13694781?pdf=render",
  "pmcid": "PMC13694781",
  "pmid": "42927136",
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1hpgynvhs3vv8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42927136",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42927136"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Traumatic Brain Injury and Neurovascular Disturbances",
      "subfield": "neurology"
    }
  ],
  "title": "Kynurenine pathway activation following moderate-to-severe traumatic brain injury with hemorrhagic shock and the effects of aeromedical evacuation.",
  "title_text": "Kynurenine pathway activation following moderate-to-severe traumatic brain injury with hemorrhagic shock and the effects of aeromedical evacuation.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/1hpgynvhs3vv8",
  "venue": "Brain, behavior, & immunity - health",
  "versions": []
}