{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:23:58Z","timestamp":1773833038836,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1IK2RX002781"],"award-info":[{"award-number":["1IK2RX002781"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["5I50RX002020"],"award-info":[{"award-number":["5I50RX002020"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["UC2ES030158"],"award-info":[{"award-number":["UC2ES030158"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"West Coast Metabolomics","doi-asserted-by":"publisher","award":["1IK2RX002781"],"award-info":[{"award-number":["1IK2RX002781"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"West Coast Metabolomics","doi-asserted-by":"publisher","award":["5I50RX002020"],"award-info":[{"award-number":["5I50RX002020"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"West Coast Metabolomics","doi-asserted-by":"publisher","award":["UC2ES030158"],"award-info":[{"award-number":["UC2ES030158"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Traumatic spinal cord injury (SCI) results in wide-ranging cellular and systemic dysfunction in the acute and chronic time frames after the injury. Chronic SCI has well-described secondary medical consequences while acute SCI has unique metabolic challenges as a result of physical trauma, in-patient recovery and other post-operative outcomes. Here, we used high resolution mass spectrometry approaches to describe the circulating lipidomic and metabolomic signatures using blood serum from mice 7 d after a complete SCI. Additionally, we probed whether the aporphine alkaloid, boldine, was able to prevent SCI-induced changes observed using these \u2018omics platforms\u2019. We found that SCI resulted in large-scale changes to the circulating lipidome but minimal changes in the metabolome, with boldine able to reverse or attenuate SCI-induced changes in the abundance of 50 lipids. Multiomic integration using xMWAS demonstrated unique network structures and community memberships across the groups.<\/jats:p>","DOI":"10.3390\/ijerph20166591","type":"journal-article","created":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T10:47:02Z","timestamp":1692269222000},"page":"6591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Boldine Alters Serum Lipidomic Signatures after Acute Spinal Cord Transection in Male Mice"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6506-7025","authenticated-orcid":false,"given":"Zachary A.","family":"Graham","sequence":"first","affiliation":[{"name":"Research Service, Birmingham VA Health Care System, Birmingham, AL 35233, USA"},{"name":"Healthspan, Resilience & Performance, Florida Institute for Human and Machine Cognition, Pensacola, FL 32502, USA"},{"name":"Department of Cell, Developmental, and Integrative Biology, University of Alabama-Birmingham, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5341-2373","authenticated-orcid":false,"given":"Jacob A.","family":"Siedlik","sequence":"additional","affiliation":[{"name":"Department of Exercise Science and Pre-Health Professions, Creighton University, Omaha, NE 68178, USA"},{"name":"School of Medicine, Creighton University, Omaha, NE 68178, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7355-7534","authenticated-orcid":false,"given":"Carlos A.","family":"Toro","sequence":"additional","affiliation":[{"name":"Spinal Cord Damage Research Center, Bronx, NY 10468, USA"},{"name":"Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Harlow","sequence":"additional","affiliation":[{"name":"Spinal Cord Damage Research Center, Bronx, NY 10468, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Cardozo","sequence":"additional","affiliation":[{"name":"Spinal Cord Damage Research Center, Bronx, NY 10468, USA"},{"name":"Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Medical Service, James J. Peters VA Medical Center, Bronx, NY 10468, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1310\/sci1804-354","article-title":"31st G. Heiner Sell Lectureship: Secondary Medical Consequences of Spinal Cord Injury","volume":"18","author":"Bauman","year":"2012","journal-title":"Top. Spinal Cord Inj. Rehabil."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"256ra137","DOI":"10.1126\/scitranslmed.3009430","article-title":"Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans","volume":"6","author":"Kobayakawa","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1089\/neu.2009.1156","article-title":"Acute Management of Nutritional Demands after Spinal Cord Injury","volume":"28","author":"Casha","year":"2011","journal-title":"J. Neurotrauma"},{"key":"ref_4","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_5","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_6","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41586-022-04828-5","article-title":"An exercise-inducible metabolite that suppresses feeding and obesity","volume":"606","author":"Li","year":"2022","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.cmet.2018.03.020","article-title":"12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake","volume":"27","author":"Stanford","year":"2018","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Peng, J., Zeng, J., Cai, B., Yang, H., Cohen, M.J., Chen, W., Sun, M.-W., Lu, C.D., and Jiang, H. (2014). Establishment of Quantitative Severity Evaluation Model for Spinal Cord Injury by Metabolomic Fingerprinting. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093736"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"38718","DOI":"10.1038\/srep38718","article-title":"Parallel Metabolomic Profiling of Cerebrospinal Fluid and Serum for Identifying Biomarkers of Injury Severity after Acute Human Spinal Cord Injury","volume":"6","author":"Wu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1163436","DOI":"10.3389\/fncel.2023.1163436","article-title":"Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury","volume":"17","author":"Toro","year":"2023","journal-title":"Front Cell Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1002\/glia.23182","article-title":"Inhibition of glial hemichannels by boldine treatment reduces neuronal suffering in a murine model of Alzheimer\u2019s disease","volume":"65","author":"Yi","year":"2017","journal-title":"Glia"},{"key":"ref_12","first-page":"593672","article-title":"Boldine Prevents Renal Alterations in Diabetic Rats","volume":"2013","author":"Vielma","year":"2013","journal-title":"J. Diabetes Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16229","DOI":"10.1073\/pnas.1312331110","article-title":"De novo expression of connexin hemichannels in denervated fast skeletal muscles leads to atrophy","volume":"110","author":"Cea","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1016\/j.bbadis.2016.07.003","article-title":"Dexamethasone-induced muscular atrophy is mediated by functional expression of connexin-based hemichannels","volume":"1862","author":"Cea","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1016\/j.bbadis.2019.06.014","article-title":"De novo expression of functional connexins 43 and 45 hemichannels increases sarcolemmal permeability of skeletal myofibers during endotoxemia","volume":"1865","author":"Cea","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/s41467-019-14063-8","article-title":"Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation","volume":"11","author":"Cisterna","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cea, L.A., V\u00e1squez, W., Hern\u00e1ndez-Salinas, R., Vielma, A.Z., Castillo-Ruiz, M., Velarde, V., Salgado, M., and S\u00e1ez, J.C. (2023). Skeletal Muscle Atrophy Induced by Diabetes Is Mediated by Non-Selective Channels and Prevented by Boldine. Biomolecules, 13.","DOI":"10.3390\/biom13040708"},{"key":"ref_18","unstructured":"National Spinal Cord Injury Statistical Center (2021). Facts and Figures at a Glance, University of Alabama at Birmingham. Available online: https:\/\/www.nscisc.uab.edu\/Public\/Facts%20and%20Figures%20-%202021.pdf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1682\/JRRD.2010.11.0220","article-title":"Who are the women and men in Veterans Health Administration\u2019s current spinal cord injury population?","volume":"49","author":"Curtin","year":"2012","journal-title":"J. Rehabil. Res. Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1089\/neu.2015.4058","article-title":"A Soluble Activin Receptor IIB Fails to Prevent Muscle Atrophy in a Mouse Model of Spinal Cord Injury","volume":"33","author":"Graham","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fiehn, O., Garvey, W.T., Newman, J.W., Lok, K.H., Hoppel, C.L., and Adams, S.H. (2010). Plasma Metabolomic Profiles Reflective of Glucose Homeostasis in Non-Diabetic and Type 2 Diabetic Obese African-American Women. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015234"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"W388","DOI":"10.1093\/nar\/gkab382","article-title":"MetaboAnalyst 5.0: Narrowing the gap between raw spectra and functional insights","volume":"49","author":"Pang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_23","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_24","doi-asserted-by":"crossref","unstructured":"Skogerson, K., Wohlgemuth, G., Barupal, D.K., and Fiehn, O. (2011). The volatile compound BinBase mass spectral database. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-321"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/bioinformatics\/btx656","article-title":"xMWAS: A data-driven integration and differential network analysis tool","volume":"34","author":"Uppal","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rohart, F., Gautier, B., Singh, A., and L\u00ea Cao, K.-A. (2017). mixOmics: An R package for \u2018omics feature selection and multiple data integration. PLoS Comput. Biol., 13.","DOI":"10.1101\/108597"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"P10008","DOI":"10.1088\/1742-5468\/2008\/10\/P10008","article-title":"Fast unfolding of communities in large networks","volume":"2008","author":"Blondel","year":"2008","journal-title":"J. Stat. Mech. Theory Exp."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.3390\/ijms15022991","article-title":"Lipidomic Analysis of Serum from High Fat Diet Induced Obese Mice","volume":"15","author":"Eisinger","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrm2330","article-title":"Membrane lipids: Where they are and how they behave","volume":"9","author":"Voelker","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4019","DOI":"10.1021\/jacs.6b11760","article-title":"Calcium Directly Regulates Phosphatidylinositol 4,5-Bisphosphate Headgroup Conformation and Recognition","volume":"139","author":"Bilkova","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.bbamem.2017.04.006","article-title":"The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease","volume":"1859","author":"Kennelly","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.bbamcr.2018.04.012","article-title":"Sphingolipid-mediated calcium signaling and its pathological effects","volume":"1865","author":"Pulli","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1172\/JCI90608","article-title":"Cell biology of spinal cord injury and repair","volume":"127","author":"Burda","year":"2017","journal-title":"J. Clin. Investig."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/20\/16\/6591\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:35:44Z","timestamp":1760128544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/20\/16\/6591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,17]]},"references-count":33,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["ijerph20166591"],"URL":"https:\/\/doi.org\/10.3390\/ijerph20166591","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.06.05.543746","asserted-by":"object"}]},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,17]]}}}