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Using principal component analysis (PCA) and Orthogonal Partial Least Squares Discriminatory Analysis (OPLS-DA), we sought to discover how SCI severity and location acutely affect the nuclear magnetic resonance-acquired metabolome of the blood, spinal cord, and liver at 6\u2009h post-SCI in mice. Unsupervised PCA of the spinal cord metabolome separated mild (30\u00a0kdyne) and severe (70\u00a0kdyne) contusion injury groups but did not distinguish between lesion level. However, OPLS-DA could discriminate thoracic level T2 from T9 lesions in both blood plasma (accuracy 86\u2009\u00b1\u20096%) and liver (accuracy 89\u2009\u00b1\u20095%) samples. These differences were dependent on alterations in energy metabolites (lactate and glucose), lipoproteins, and lipids. Lactate was the most discriminatory between mild and severe injury at T2, whereas overlapping valine\/proline resonances were most discriminatory between injury severities at T9. Plasma lactate correlated with blood-spinal cord barrier breakdown and plasma glucose with microglial density. We propose that peripheral biofluid metabolites can serve as biomarkers of SCI severity and associated pathology at the lesion site; their predictive value is most accurate when the injury level is also considered.<\/jats:p>","DOI":"10.1093\/jnen\/nlaf082","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T11:19:46Z","timestamp":1753096786000},"page":"24-38","source":"Crossref","is-referenced-by-count":3,"title":["Lesion level and severity acutely influence metabolomic profiles in spinal cord injury"],"prefix":"10.1093","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8501-2160","authenticated-orcid":false,"given":"Abi G","family":"Yates","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Medical Sciences Division, University of Oxford , Oxford,","place":["United Kingdom"]},{"name":"School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland , Brisbane, 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