{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:28:42Z","timestamp":1788982122500,"version":"build-2803163510"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>We aimed to compare the prevalence and multimodal associations of mitochondrial dysfunction as defined by published cerebral-microdialysis-based criteria versus our novel multimodality-monitoring-based criteria in acute traumatic brain injury patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We retrospectively analyzed neurocritical care monitoring data from 619 acute traumatic brain injury patients. Monitoring modalities included cerebral microdialysis, intracranial pressure, brain tissue oxygenation, cerebral perfusion pressure, and the pressure reactivity index. The cerebral-microdialysis-based criteria we compared combine an elevated lactate\/pyruvate ratio (25 or 30) with raised concentrations of lactate (2.5\u2009mM) or pyruvate (70 \u03bcM or 120 \u03bcM). Our multimodality-monitoring-based criteria comprise a consistent lactate\/pyruvate ratio\u2009&gt;\u200925 with intracranial pressure\u2009\u2264\u200920 mmHg, brain tissue oxygenation\u2009\u2265\u200915 mmHg, a pressure reactivity index\u2009\u2264\u20090.3, and cerebral glucose\u2009\u2265\u20091.0\u2009mM.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Across 592 analyzable patients, a lactate\/pyruvate ratio\u2009&gt;\u200925 was common, with a median prevalence of 48.9% (41.5% with consistency) and a U-shaped, bimodal distribution. A lactate\/pyruvate ratio\u2009&gt;\u200925 was associated with lower glucose and higher glycerol, and when accompanied by high pyruvate (&gt; 120 \u03bcM), this derangement was further distinguished by higher glutamate and cerebral perfusion pressure. Using multimodal criteria on a cohort of 268 patients, consistent mitochondrial dysfunction was identified in 25.7% to 41.0% of patients, often in the absence of other physiological derangements.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Many acute traumatic brain injury patients constantly demonstrate neurometabolic derangements, among which clinical mitochondrial dysfunction is highly prevalent despite normal cerebral pressure, oxygenation, and perfusion. There is necessity for targeted, neurometabolic therapies in neurocritical care that address this abnormality.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0331310","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T17:48:08Z","timestamp":1756835288000},"page":"e0331310","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Defining metabolic abnormalities in acute human traumatic brain injury with cerebral microdialysis and multimodality monitoring"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3078-3001","authenticated-orcid":true,"given":"Michael 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