{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:58:49Z","timestamp":1790024329562,"version":"4.0.1"},"reference-count":118,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019286","name":"Ajman University Internal Research Grant","doi-asserted-by":"publisher","award":["2022-IRG-DEN-12"],"award-info":[{"award-number":["2022-IRG-DEN-12"]}],"id":[{"id":"10.13039\/501100019286","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ajman University","award":["2022-IRG-DEN-12"],"award-info":[{"award-number":["2022-IRG-DEN-12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brachial plexus root avulsion [BPRA] and concomitant spinal cord injury [SCI] represent devastating injuries that come with limited hope for recovery owing to the adult spinal cord\u2019s loss of intrinsic ability to spontaneously regenerate. BPRA\/SCI is an enormous public health issue the world over, and its catastrophic impact goes beyond the patient, the family, businesses, and national health budgets, draining billions of dollars annually. The rising population and economic growth have seen the incidence of SCI surging. Genomic, transcriptomic, and proteomic studies have yielded loads of information on the various molecular events that precede, regulate, and support both regenerative and degenerative pathways post-SCI. Metabolomics, on the other hand, comes in as the search for a cure and the objective monitoring of SCI severity and prognosis remains on the horizon. Despite the large number of review articles on metabolomics and its application fields such as in cancer and diabetes research, there is no comprehensive review on metabolite profiling to study disease mechanisms, biomarkers, or neuroprotection in SCI. First, we present a short review on BPRA\/SCI. Second, we discuss potential benefits of metabolomics as applied in BPRA\/SCI cases. Next, a look at the analytical techniques that are used in metabolomics. Next, we present an overview of the studies that have used metabolomics to reveal SCI metabolic fingerprints and point out areas of further investigation. Finally, we discuss future research directions.<\/jats:p>","DOI":"10.3390\/ijms26146864","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T11:25:17Z","timestamp":1752751517000},"page":"6864","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Utility of Metabolomics in Spinal Cord Injury: Opportunities for Biomarker Discovery and Neuroprotection"],"prefix":"10.3390","volume":"26","author":[{"given":"Prince Last Mudenda","family":"Zilundu","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anesuishe Blessings","family":"Gatsi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Zimbabwe, Harare MP167, Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapiwa","family":"Chapupu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Zimbabwe, Harare MP167, Zimbabwe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Sun Yat-sen School of Medicine, Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.2106\/JBJS.J.00922","article-title":"Concomitant Traumatic Spinal Cord and Brachial Plexus Injuries in Adult Patients","volume":"93","author":"Rhee","year":"2011","journal-title":"J. Bone Jt. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11068-009-9040-4","article-title":"Differences in c-jun and nNOS expression levels in motoneurons following different kinds of axonal injury in adult rats","volume":"36","author":"Zhou","year":"2008","journal-title":"Brain Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zilundu, P.L.M., Xu, X., Liaquat, Z., Wang, Y., Zhong, K., Fu, R., and Zhou, L. (2021). Long-Term Suppression of c-Jun and nNOS Preserves Ultrastructural Features of Lower Motor Neurons and Forelimb Function after Brachial Plexus Roots Avulsion. Cells, 10.","DOI":"10.3390\/cells10071614"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1111\/ejn.13089","article-title":"Clinical and neurobiological advances in promoting regeneration of the ventral root avulsion lesion","volume":"43","author":"Eggers","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1097\/WCO.0000000000001124","article-title":"Traumatic brachial plexus injury: Diagnosis and treatment","volume":"35","author":"Wu","year":"2022","journal-title":"Curr. Opin. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4103\/0028-3886.177597","article-title":"Adult brachial plexus injuries: Surgical strategies and approaches","volume":"64","author":"Sinha","year":"2016","journal-title":"Neurol. India"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.jhsa.2023.01.019","article-title":"Indications and Technique for the Use of Intraoperative Neuromonitoring in Brachial Plexus Surgery","volume":"48","author":"Zelenski","year":"2023","journal-title":"J. Hand Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1175.e1","DOI":"10.1016\/j.jhsa.2023.07.012","article-title":"Prespinal Versus Conventional Hemicontralateral C7 Nerve Transfer in the Treatment of Total Brachial Plexus Roots Avulsion Injuries: A Retrospective Study With a Minimum Follow-Up Period of 4 Years","volume":"48","author":"Li","year":"2023","journal-title":"J. Hand Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.tice.2016.05.008","article-title":"Stem cell based therapies for spinal cord injury","volume":"48","author":"Muheremu","year":"2016","journal-title":"Tissue Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1089\/neu.2006.23.920","article-title":"Survival of Injured Spinal Motoneurons in Adult Rat upon Treatment with Glial Cell Line\u2013Derived Neurotrophic Factor at 2 Weeks but Not at 4 Weeks after Root Avulsion","volume":"23","author":"Zhou","year":"2006","journal-title":"J. Neurotrauma"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nature13974","article-title":"Modulation of the proteoglycan receptor PTP\u03c3 promotes recovery after spinal cord injury","volume":"518","author":"Lang","year":"2015","journal-title":"Nature"},{"key":"ref_12","first-page":"817","article-title":"Application of stem cells, growth factors, small molecules, and biological macromolecules on nerve regeneration: A review and future direction","volume":"73","author":"Niknami","year":"2023","journal-title":"Int. J. Polym. Mater. Polym. Biomater."},{"key":"ref_13","first-page":"68","article-title":"Spinal cord conduits for spinal cord injury regeneration","volume":"4","author":"Ma","year":"2023","journal-title":"Eng. Regen."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Alizadeh, A., Dyck, S.M., and Karimi-Abdolrezaee, S. (2019). Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00282"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"50","DOI":"10.46292\/sci2702-50","article-title":"Experimental Treatments for Spinal Cord Injury: What you Should Know","volume":"27","author":"Failli","year":"2021","journal-title":"Top. Spinal Cord Inj. Rehabil."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e11505","DOI":"10.15252\/emmm.201911505","article-title":"Therapeutic repair for spinal cord injury: Combinatory approaches to address a multifaceted problem","volume":"12","author":"Griffin","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/1545968312457825","article-title":"Metabolic changes in the spinal cord after brachial plexus root re-implantation","volume":"27","author":"Kachramanoglou","year":"2013","journal-title":"Neurorehabilit. Neural Repair"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhang, J.-L., Xian, H., Zhao, R., Luo, C., Xie, R.-G., Tian, T., and Cong, R. (2023). Brachial plexus avulsion induced changes in gut microbiota promotes pain related anxiety-like behavior in mice. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1084494"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nature06882","article-title":"Human metabolic phenotype diversity and its association with diet and blood pressure","volume":"453","author":"Holmes","year":"2008","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1152\/physrev.00035.2018","article-title":"Metabolomics for Investigating Physiological and Pathophysiological Processes","volume":"99","author":"Wishart","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/j.jaci.2017.04.021","article-title":"A review of metabolomics approaches and their application in identifying causal pathways of childhood asthma","volume":"141","author":"Turi","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/mas.21627","article-title":"High Resolution Mass Spectrometry in Lipidomics","volume":"40","year":"2021","journal-title":"Mass Spectrom. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fujieda, Y., Ueno, S., Ogino, R., Kuroda, M., J\u00f6nsson, T.J., Guo, L., Bamba, T., Fukusaki, E., and Di Giovanni, S. (2012). Metabolite Profiles Correlate Closely with Neurobehavioral Function in Experimental Spinal Cord Injury in Rats. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043152"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1615\/CritRevBiomedEng.2013007736","article-title":"Metabolomic Fingerprinting: Challenges and Opportunities","volume":"41","author":"Kosmides","year":"2013","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Blaurock, J., Baumann, S., Grunewald, S., Schiller, J., and Engel, K.M. (2022). Metabolomics of Human Semen: A Review of Different Analytical Methods to Unravel Biomarkers for Male Fertility Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169031"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hyv\u00e4rinen, E., Savolainen, M., Mikkonen, J.J.W., and Kullaa, A.M. (2021). Salivary Metabolomics for Diagnosis and Monitoring Diseases: Challenges and Possibilities. Metabolites, 11.","DOI":"10.3390\/metabo11090587"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kiseleva, O., Kurbatov, I., Ilgisonis, E., and Poverennaya, E. (2021). Defining Blood Plasma and Serum Metabolome by GC-MS. Metabolites, 12.","DOI":"10.3390\/metabo12010015"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Saoi, M., and Britz-McKibbin, P. (2021). New Advances in Tissue Metabolomics: A Review. Metabolites, 11.","DOI":"10.3390\/metabo11100672"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3322\/caac.21670","article-title":"Metabolomics in cancer research and emerging applications in clinical oncology","volume":"71","author":"Schmidt","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_30","first-page":"e1795","article-title":"Metabolomics in oncology","volume":"6","author":"Suri","year":"2023","journal-title":"Cancer Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"188-OR","DOI":"10.2337\/db23-188-OR","article-title":"188-OR: Circulating metabolites and type 2 diabetes [T2D] risk\u2014An integrated metabolomics and genetics study of ~23,000 adults","volume":"72","author":"Li","year":"2023","journal-title":"Diabetes"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Shahisavandi, M., Wang, K., Ghanbari, M., and Ahmadizar, F. (2023). Exploring Metabolomic Patterns in Type 2 Diabetes Mellitus and Response to Glucose-Lowering Medications\u2014Review. Genes, 14.","DOI":"10.3390\/genes14071464"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chaiyachat, P., Kaewseekhao, B., Chaiprasert, A., Kamolwat, P., Nonghanphithak, D., Phetcharaburanin, J., Sirichoat, A., Ong, R.T.-H., and Faksri, K. (2023). Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-35882-2"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"147704","DOI":"10.1016\/j.brainres.2021.147704","article-title":"Metabolomics in degenerative brain diseases","volume":"1773","author":"Escobar","year":"2021","journal-title":"Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1016\/j.apsb.2023.05.021","article-title":"Metabolomics in drug research and development: The recent advances in technologies and applications","volume":"13","author":"Pang","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41392-023-01399-3","article-title":"Small molecule metabolites: Discovery of biomarkers and therapeutic targets","volume":"8","author":"Qiu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s41232-022-00245-3","article-title":"Quercetin enhances survival and axonal regeneration of motoneurons after spinal root avulsion and reimplantation: Experiments in a rat model of brachial plexus avulsion","volume":"42","author":"Huang","year":"2022","journal-title":"Inflamm. Regen."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3892\/mmr.2021.12056","article-title":"Acute spinal cord injury: Pathophysiology and pharmacological intervention","volume":"23","author":"Zhang","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1750-1326-7-6","article-title":"Spinal cord trauma and the molecular point of no return","volume":"7","author":"Yip","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s12031-015-0588-4","article-title":"Identification of the Avulsion-Injured Spinal Motoneurons","volume":"57","author":"Tan","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.neuroscience.2011.04.070","article-title":"C-jun phosphorylation contributes to down regulation of neuronal nitric oxide synthase protein and motoneurons death in injured spinal cords following root-avulsion of the brachial plexus","volume":"189","author":"Wang","year":"2011","journal-title":"Neuroscience"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13063-017-1870-2","article-title":"Why clinical trial outcomes fail to translate into benefits for patients","volume":"18","author":"Heneghan","year":"2017","journal-title":"Trials"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Guest, J., Datta, N., Jimsheleishvili, G., and Gater, D.R. (2022). Pathophysiology, Classification and Comorbidities after Traumatic Spinal Cord Injury. J. Pers. Med., 12.","DOI":"10.3390\/jpm12071126"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dietz, V.A., Roberts, N., Knox, K., Moore, S., Pitonak, M., Barr, C., Centeno, J., Leininger, S., New, K.C., and Nowell, P. (2022). Fighting for recovery on multiple fronts: The past, present, and future of clinical trials for spinal cord injury. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.977679"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Emwas, A.-H. (2015). Theory and Applications of NMR-Based Metabolomics in Human Disease Diagnosis, Bentham Science Publishers.","DOI":"10.2174\/9781608059621115010005"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gonzalez-Covarrubias, V., Mart\u00ednez-Mart\u00ednez, E., and del Bosque-Plata, L. (2022). The Potential of Metabolomics in Biomedical Applications. Metabolites, 12.","DOI":"10.3390\/metabo12020194"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.copbio.2014.04.006","article-title":"After the Feature Presentation: Technologies Bridging Untargeted Metabolomics and Biology","volume":"28","author":"Cho","year":"2014","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e1230","DOI":"10.1002\/cl2.1230","article-title":"PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis","volume":"18","author":"Haddaway","year":"2022","journal-title":"Campbell Syst. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.freeradbiomed.2022.10.303","article-title":"LC\u2013MS\/MS-based arachidonic acid metabolomics in acute spinal cord in\u2019jury reveals the upregulation of 5-LOX and COX-2 products","volume":"193","author":"Pang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.jpain.2020.09.001","article-title":"Molecular Pathways Linking Oxylipins to Nociception in Rats","volume":"22","author":"Domenichiello","year":"2021","journal-title":"J. Pain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.jpain.2021.11.009","article-title":"Morphine resistance in spinal cord injury-related neuropathic pain in rats is associated with alterations in dopamine and dopamine-related metabolomics","volume":"23","author":"Rodgers","year":"2022","journal-title":"J. Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12987-024-00514-y","article-title":"Investigating post-traumatic syringomyelia and local fluid osmoregulation via a rat model","volume":"21","author":"Pukale","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5591582","DOI":"10.1155\/2021\/5591582","article-title":"EZH2 Mediates miR-146a-5p\/HIF-1\u03b1 to Alleviate Inflammation and Glycolysis after Acute Spinal Cord Injury","volume":"2021","author":"Ni","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhang, J., Ying, X., Hu, R., Huang, Y., Wang, R., Wu, L., Han, D., Ma, R., and He, K. (Biomol. Biomed., 2025). Metagenomic and metabolomic analysis of gut microbiome\u2019s role in spinal cord injury recovery in rats, Biomol. Biomed., Online ahead of print.","DOI":"10.17305\/bb.2025.12164"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Liang, W., Zhang, T., Zhang, M., Gao, J., Huang, R., Huang, X., Chen, J., Cheng, L., Zhang, L., and Huang, Z. (2024). Daphnetin Ameliorates Neuropathic Pain via Regulation of Microglial Responses and Glycerophospholipid Metabolism in the Spinal Cord. Pharmaceuticals, 17.","DOI":"10.3390\/ph17060789"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yuan, Z., Zhao, X., Zhang, Y., Jiao, Y., Liu, Y., Gao, C., Zhang, J., Ma, Y., Wang, Z., and Li, T. (2025). Using Integrated Network Pharmacology and Metabolomics to Reveal the Mechanisms of the Combined Intervention of Ligustrazine and Sinomenine in CCI-Induced Neuropathic Pain Rats. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062604"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1186\/s12967-023-04648-9","article-title":"Lycium Barbarum Glycopeptide alleviates neuroinflammation in spinal cord injury via modulating docosahexaenoic acid to inhibiting MAPKs\/NF-kB and pyroptosis pathways","volume":"21","author":"Jiang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zeng, Z., Li, M., Jiang, Z., Lan, Y., Chen, L., Chen, Y., Li, H., Hui, J., Zhang, L., and Hu, X. (2022). Integrated Transcriptomic and Metabolomic Profiling Reveals Dysregulation of Purine Metabolism During the Acute Phase of Spinal Cord Injury in Rats. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.1066528"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"88","DOI":"10.5213\/inj.2346068.034","article-title":"Time-Dependent Changes in the Bladder Muscle Metabolome After Traumatic Spinal Cord Injury in Rats Using Metabolomics","volume":"27","author":"Liu","year":"2023","journal-title":"Int. Neurourol. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e1051","DOI":"10.1016\/j.wneu.2019.07.077","article-title":"Metabolic Changes in Serum in the Rat Model of Cauda Equina Injury","volume":"130","author":"Zhang","year":"2019","journal-title":"World Neurosurg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s12031-021-01903-w","article-title":"Parallel Metabolomic Profiling of Cerebrospinal Fluid, Plasma, and Spinal Cord to Identify Biomarkers for Spinal Cord Injury","volume":"72","author":"Yang","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"fcad091","DOI":"10.1093\/braincomms\/fcad091","article-title":"Cervical spinal cord injury leads to injury and altered metabolism in the lungs","volume":"5","author":"Huffman","year":"2023","journal-title":"Brain Commun."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Wang, Z., Xie, Z., Zhang, Z., Zhou, W., Guo, B., and Li, M. (2024). Multi-platform omics sequencing dissects the atlas of plasma-derived exosomes in rats with or without depression-like behavior after traumatic spinal cord injury. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 132.","DOI":"10.1016\/j.pnpbp.2024.110987"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"111170","DOI":"10.1016\/j.intimp.2023.111170","article-title":"Integration of microbiota and metabolomics reveals the analgesic mechanisms of emodin against neuropathic pain","volume":"125","author":"Wang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10547","DOI":"10.1096\/fj.202000447R","article-title":"Regional cerebral metabolic levels and turnover in awake rats after acute or chronic spinal cord injury","volume":"34","author":"Wu","year":"2020","journal-title":"FASEB J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3892\/etm.2025.12867","article-title":"In situ mass spectrometry imaging reveals metabolite alterations in gray and white matter after spinal cord injury","volume":"29","author":"Lyu","year":"2025","journal-title":"Exp. Ther. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11731","DOI":"10.1523\/JNEUROSCI.1395-17.2017","article-title":"Maresin 1 Promotes Inflammatory Resolution, Neuroprotection, and Functional Neurological Recovery After Spinal Cord Injury","volume":"37","author":"Gronert","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13041-021-00765-y","article-title":"Alterations in the gut microbiota and metabolite profiles in the context of neuropathic pain","volume":"14","author":"Chen","year":"2021","journal-title":"Mol. Brain"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Shi, Y., Zheng, M., Luo, Y., Li, J., Ouyang, F., Zhao, Y., Wang, J., Ma, Z., Meng, C., and Bi, Y. (2024). Targeting transcription factor pu.1 for improving neurologic outcomes after spinal cord injury. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1418615"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"fcab058","DOI":"10.1093\/braincomms\/fcab058","article-title":"Rostro-caudal different energy metabolism leading to differences in degeneration in spinal cord injury","volume":"3","author":"Ohnishi","year":"2021","journal-title":"Brain Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5662","DOI":"10.7150\/thno.96374","article-title":"MCT1-mediated endothelial cell lactate shuttle as a target for promoting axon regeneration after spinal cord injury","volume":"14","author":"Shi","year":"2024","journal-title":"Theranostics"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1089\/neu.2018.6144","article-title":"Key Glycolytic Metabolites in Paralyzed Skeletal Muscle Are Altered Seven Days after Spinal Cord Injury in Mice","volume":"36","author":"Graham","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.4103\/1673-5374.355769","article-title":"Alterations in gut microbiota are related to metabolite profiles in spinal cord injury","volume":"18","author":"Kang","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e14826","DOI":"10.1111\/cns.14826","article-title":"Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury","volume":"30","author":"Zhang","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Rong, Z.-J., Cai, H.-H., Wang, H., Liu, G.-H., Zhang, Z.-W., Chen, M., and Huang, Y.-L. (2022). Ursolic Acid Ameliorates Spinal Cord Injury in Mice by Regulating Gut Microbiota and Metabolic Changes. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.872935"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1089\/neu.2024.0385","article-title":"Evolution of Lipid Metabolism in the Injured Mouse Spinal Cord","volume":"42","author":"Scholpa","year":"2025","journal-title":"J. Neurotrauma"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13073-025-01434-8","article-title":"Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury","volume":"17","author":"Zhou","year":"2025","journal-title":"Genome Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1152\/physiolgenomics.00129.2022","article-title":"Assessing the impact of boldine on the gastrocnemius using multiomics profiling at 7 and 28 days post-complete spinal cord injury in young male mice","volume":"55","author":"Potter","year":"2023","journal-title":"Physiol. Genom."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e15266","DOI":"10.14814\/phy2.15266","article-title":"SS-31 does not prevent or reduce muscle atrophy 7 days after a 65 kdyne contusion spinal cord injury in young male mice","volume":"10","author":"Graham","year":"2022","journal-title":"Physiol. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"109988","DOI":"10.1016\/j.neuropharm.2024.109988","article-title":"Common alterations in parallel metabolomic profiling of serum and spinal cord and mechanistic studies on neuropathic pain following PPAR\u03b1 administration","volume":"254","author":"Zhao","year":"2024","journal-title":"Neuropharmacology"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Jing, Y., Yang, D., Bai, F., Wang, Q., Zhang, C., Yan, Y., Li, Z., Li, Y., Chen, Z., and Li, J. (2023). Spinal cord injury-induced gut dysbiosis influences neurological recovery partly through short-chain fatty acids. NPJ Biofilms Microbio., 9.","DOI":"10.1038\/s41522-023-00466-5"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.cca.2018.02.011","article-title":"Proton NMR based serum metabolic profile correlates with the neurological recovery in treated acute spinal cord injury [ASCI] subjects: A pilot study","volume":"480","author":"Singh","year":"2018","journal-title":"Clin. Chim. Acta"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41394-018-0121-4","article-title":"Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: A pilot, randomized safety and feasibility trial","volume":"4","author":"Kulkarni","year":"2018","journal-title":"Spinal Cord Ser. Cases"},{"key":"ref_84","first-page":"1","article-title":"1H NMR urine metabolomics is an effective prognostic indicator in acute spinal cord injury [ASCI]: A prospective case-control study","volume":"4","author":"Singh","year":"2020","journal-title":"J. Metabolom. Syst. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ibneur.2021.02.007","article-title":"Urinary biomarkers indicative of recovery from spinal cord injury: A pilot study","volume":"10","author":"Bykowski","year":"2021","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.apmr.2021.03.043","article-title":"Gut Microbiome Composition and Serum Metabolome Profile Among Individuals With Spinal Cord Injury and Normal Glucose Tolerance or Prediabetes\/Type 2 Diabetes","volume":"103","author":"Li","year":"2022","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Bykowski, E.A., Petersson, J.N., Dukelow, S., Ho, C., Debert, C.T., Montina, T., and Metz, G.A.S. (2023). Identification of Serum Metabolites as Prognostic Biomarkers Following Spinal Cord Injury: A Pilot Study. Metabolites, 13.","DOI":"10.3390\/metabo13050605"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13041-023-01014-0","article-title":"The gut microbiota and metabolite profiles are altered in patients with spinal cord injury","volume":"16","author":"Kong","year":"2023","journal-title":"Mol. Brain"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41394-025-00698-x","article-title":"A preliminary study on the changes of fecal short chain fatty acids in patients with traumatic spinal cord injury in the chronic phase","volume":"11","author":"Zhang","year":"2025","journal-title":"Spinal Cord Ser. Cases"},{"key":"ref_90","unstructured":"\u00c1lvarez-Mu\u00f1oz, D., and Farr\u00e9, M. (2020). Chapter 2\u2014Analytical techniques in metabolomics. Environmental Metabolomics, Elsevier."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.4155\/bio-2019-0014","article-title":"Analytical techniques for metabolomic studies: A review","volume":"11","author":"Segers","year":"2019","journal-title":"Bioanalysis"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Huang, K., Thomas, N., Gooley, P.R., and Armstrong, C.W. (2022). Systematic Review of NMR-Based Metabolomics Practices in Human Disease Research. Metabolites, 12.","DOI":"10.3390\/metabo12100963"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Ivanisevic, J., and Want, E.J. (2019). From Samples to Insights into Metabolism: Uncovering Biologically Relevant Information in LC-HRMS Metabolomics Data. Metabolites, 9.","DOI":"10.3390\/metabo9120308"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41392-023-01380-0","article-title":"To metabolomics and beyond: A technological portfolio to investigate cancer metabolism","volume":"8","author":"Danzi","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1002\/mas.21858","article-title":"What is the role of current mass spectrometry in pharmaceutical analysis?","volume":"43","author":"Khalikova","year":"2024","journal-title":"Mass Spectrom. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Ahmed, F., Eticha, T., Hymete, A., and Ashenef, A. (2023). Principles and Applications of Ultra-High-Performance Liquid Chromatography. IntechOpen.","DOI":"10.5772\/intechopen.110540"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00216-021-03290-y","article-title":"Recent [2018\u20132020] development in capillary electrophoresis","volume":"414","author":"Gao","year":"2022","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nmeth.4112","article-title":"Global metabolomics","volume":"14","author":"Doerr","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2147\/TACG.S125962","article-title":"Maple syrup urine disease: Mechanisms and management","volume":"10","author":"Blackburn","year":"2017","journal-title":"Appl. Clin. Genet."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Chou, F.-J., Liu, Y., Lang, F., and Yang, C. (2021). D-2-Hydroxyglutarate in glioma biology. Cells, 10.","DOI":"10.3390\/cells10092345"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrd.2016.32","article-title":"Emerging applications of metabolomics in drug discovery and precision medicine","volume":"15","author":"Wishart","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/mas.21548","article-title":"Metabolomics toward personalized medicine","volume":"38","author":"Jacob","year":"2019","journal-title":"Mass Spectrom. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/s13063-020-04273-7","article-title":"Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: Study protocol for a randomized controlled trial","volume":"21","author":"Demirel","year":"2020","journal-title":"Trials"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wu, Y., Streijger, F., Wang, Y., Lin, G., Christie, S., Mac-Thiong, J.-M., Parent, S., Bailey, C.S., Paquette, S., and Boyd, M.C. (2016). Parallel Metabolomic Profiling of Cerebrospinal Fluid and Serum for Identifying Biomarkers of Injury Severity after Acute Human Spinal Cord Injury. Sci. Rep., 6.","DOI":"10.1038\/srep38718"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"103751","DOI":"10.1016\/j.drudis.2023.103751","article-title":"Metabolomics and lipidomics strategies in modern drug discovery and development","volume":"28","author":"Astarita","year":"2023","journal-title":"Drug Discov. Today"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e792","DOI":"10.1002\/mco2.792","article-title":"Metabolomics-driven approaches for identifying therapeutic targets in drug discovery","volume":"5","author":"Pan","year":"2024","journal-title":"Medcomm"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"101144","DOI":"10.1016\/j.jpha.2024.101144","article-title":"Elucidating the role of artificial intelligence in drug development from the perspective of drug-target interactions","volume":"15","author":"Wang","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1186\/s12967-022-03809-6","article-title":"Metabolomic profiles of metformin in breast cancer survivors: A pooled analysis of plasmas from two randomized placebo-controlled trials","volume":"20","author":"Bellerba","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Pinu, F.R., Beale, D.J., Paten, A.M., Kouremenos, K., Swarup, S., Schirra, H.J., and Wishart, D. (2019). Systems Biology and Multi-Omics Integration: Viewpoints from the Metabolomics Research Community. Metabolites, 9.","DOI":"10.3390\/metabo9040076"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Olivier, M., Asmis, R., Hawkins, G.A., Howard, T.D., and Cox, L.A. (2019). The need for multi-omics biomarker signatures in precision medicine. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194781"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1021\/acs.analchem.2c04606","article-title":"NMR Metabolomics Methods for Investigating Disease","volume":"95","author":"Gowda","year":"2023","journal-title":"Anal. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Hsieh, W.-C., Budiarto, B.R., Wang, Y.-F., Lin, C.-Y., Gwo, M.-C., So, D.K., Tzeng, Y.-S., and Chen, S.-Y. (2022). Spatial multi-omics analyses of the tumor immune microenvironment. J. Biomed. Sci., 29.","DOI":"10.1186\/s12929-022-00879-y"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Peng, R., Zhang, L., Xie, Y., Guo, S., Cao, X., and Yang, M. (2024). Spatial multi-omics analysis of the microenvironment in traumatic spinal cord injury: A narrative review. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1432841"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Wishart, D.S., Cheng, L.L., Copi\u00e9, V., Edison, A.S., Eghbalnia, H.R., Hoch, J.C., Gouveia, G.J., Pathmasiri, W., Powers, R., and Schock, T.B. (2022). NMR and Metabolomics-A Roadmap for the Future. Metabolites, 12.","DOI":"10.3390\/metabo12080678"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"117163","DOI":"10.1016\/j.trac.2023.117287","article-title":"Recent advances in high-throughput biofluid metabotyping by direct infusion and ambient ionization mass spectrometry","volume":"168","author":"Plekhova","year":"2023","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.1021\/acs.analchem.7b05291","article-title":"In Vivo Real-Time Monitoring System Using Probe Electrospray Ionization\/Tandem Mass Spectrometry for Metabolites in Mouse Brain","volume":"90","author":"Zaitsu","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"12852","DOI":"10.1002\/anie.202100923","article-title":"In Vivo Subcellular Mass Spectrometry Enables Proteo-Metabolomic Single-Cell Systems Biology in a Chordate Embryo Developing to a Normally Behaving Tadpole [X. laevis]*","volume":"60","author":"Li","year":"2021","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Richter, J.K., Vallesi, V., Z\u00f6lch, N., Chan, K.L., Hunkeler, N., Abramovic, M., Hashagen, C., Christiaanse, E., Shetty, G., and Verma, R.K. (2023). Metabolic profile of complete spinal cord injury in pons and cerebellum: A 3T 1H MRS study. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-34326-1"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6864\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:11:17Z","timestamp":1760033477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/14\/6864"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,17]]},"references-count":118,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ijms26146864"],"URL":"https:\/\/doi.org\/10.3390\/ijms26146864","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,17]]}}}