{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:04:50Z","timestamp":1789124690466,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T00:00:00Z","timestamp":1653177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Child Health Research Institute","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Hypoxic-ischemic brain injury (HIBI) leads to depletion of ATP, mitochondrial dysfunction, and enhanced oxidant formation. Measurement of acylcarnitines may provide insight into mitochondrial dysfunction. Plasma acylcarnitine levels are altered in neonates after an HIBI, but individual acylcarnitine levels in the brain have not been evaluated. Additionally, it is unknown if plasma acylcarnitines reflect brain acylcarnitine changes. In this study, postnatal day 9 CD1 mouse pups were randomized to HIBI induced by carotid artery ligation, followed by 30 min at 8% oxygen, or to sham surgery and normoxia, with subgroups for tissue collection at 30 min, 24 h, or 72 h after injury (12 animals\/group). Plasma, liver, muscle, and brain (dissected into the cortex, cerebellum, and striatum\/thalamus) tissues were collected for acylcarnitine analysis by LC-MS. At 30 min after HIBI, acylcarnitine levels were significantly increased, but the differences resolved by 24 h. Palmitoylcarnitine was increased in the cortex, muscle, and plasma, and stearoylcarnitine in the cortex, striatum\/thalamus, and cerebellum. Other acylcarnitines were elevated only in the muscle and plasma. In conclusion, although plasma acylcarnitine results in this study mimic those seen previously in humans, our data suggest that the plasma acylcarnitine profile was more reflective of muscle changes than brain changes. Acylcarnitine metabolism may be a target for therapeutic intervention after neonatal HIBI, though the lack of change after 30 min suggests a limited therapeutic window.<\/jats:p>","DOI":"10.3390\/metabo12050467","type":"journal-article","created":{"date-parts":[[2022,5,22]],"date-time":"2022-05-22T07:13:57Z","timestamp":1653203637000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neonatal Hypoxic-Ischemic Brain Injury Alters Brain Acylcarnitine Levels in a Mouse Model"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7468-2444","authenticated-orcid":false,"given":"Amanda M.","family":"Dave","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Children\u2019s Hospital & Medical Center, Omaha, NE 68114, USA"},{"name":"Child Health Research Institute, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-2285","authenticated-orcid":false,"given":"Thiago C.","family":"Genaro-Mattos","sequence":"additional","affiliation":[{"name":"Child Health Research Institute, Omaha, NE 68198, USA"},{"name":"Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8690-4507","authenticated-orcid":false,"given":"Zeljka","family":"Korade","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Child Health Research Institute, Omaha, NE 68198, USA"},{"name":"Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2892-2678","authenticated-orcid":false,"given":"Eric S.","family":"Peeples","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Children\u2019s Hospital & Medical Center, Omaha, NE 68114, USA"},{"name":"Child Health Research Institute, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.earlhumdev.2010.05.010","article-title":"Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy","volume":"86","author":"Kurinczuk","year":"2010","journal-title":"Early Hum. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1053\/j.semperi.2016.09.007","article-title":"Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE)","volume":"40","author":"Natarajan","year":"2016","journal-title":"Semin. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Huang, B.Y., and Castillo, M. (2008). Hypoxic-ischemic brain injury: Imaging findings from birth to adulthood. Radiographics, 28.","DOI":"10.1148\/rg.282075066"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.plipres.2009.08.004","article-title":"Acylcarnitines: Role in brain","volume":"49","author":"Jones","year":"2010","journal-title":"Prog. Lipid Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gnoni, A., Longo, S., Gnoni, G.V., and Giudetti, A.M. (2020). Carnitine in Human Muscle Bioenergetics: Can Carnitine Supplementation Improve Physical Exercise?. Molecules, 25.","DOI":"10.3390\/molecules25010182"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fnins.2014.00040","article-title":"The mechanisms and treatment of asphyxial encephalopathy","volume":"8","author":"Wassink","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1203\/01.PDR.0000085036.07561.9C","article-title":"L-carnitine reduces brain injury after hypoxia-ischemia in newborn rats","volume":"54","author":"Wainwright","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1159\/000455041","article-title":"Neuroprotective Effects of Acetyl-L-Carnitine on Neonatal Hypoxia Ischemia-Induced Brain Injury in Rats","volume":"38","author":"Tang","year":"2016","journal-title":"Dev. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Walsh, B.H., Broadhurst, D.I., Mandal, R., Wishart, D.S., Boylan, G.B., Kenny, L.C., and Murray, D.M. (2012). The metabolomic profile of umbilical cord blood in neonatal hypoxic ischaemic encephalopathy. PLoS One, 7.","DOI":"10.1371\/journal.pone.0050520"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1203\/00006450-200101000-00024","article-title":"Postnatal changes in neonatal acylcarnitine profile","volume":"49","author":"Meyburg","year":"2001","journal-title":"Pedatric Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e15221","DOI":"10.1097\/MD.0000000000015221","article-title":"Acylcarnitine profile in neonatal hypoxic-ischemic encephalopathy: The value of butyrylcarnitine as a prognostic marker","volume":"98","author":"Cocho","year":"2019","journal-title":"Medicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"BSR20211696","DOI":"10.1042\/BSR20211696","article-title":"Mitochondrial dynamics in the neonatal brain\u2014A potential target following injury?","volume":"42","author":"Jones","year":"2022","journal-title":"Biosci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1089\/ars.2020.8093","article-title":"Hypoxic-Ischemic Encephalopathy and Mitochondrial Dysfunction: Facts, Unknowns, and Challenges","volume":"33","author":"Valez","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"McCann, M.R., De la Rosa, M.V.G., Rosania, G.R., and Stringer, K.A. (2021). L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine. Metabolites, 11.","DOI":"10.3390\/metabo11010051"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"577856","DOI":"10.3389\/fphys.2020.577856","article-title":"Long-Chain Acylcarnitines and Cardiac Excitation-Contraction Coupling: Links to Arrhythmias","volume":"11","author":"Krause","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.bbadis.2015.01.011","article-title":"Palmitoyl-carnitine increases RyR2 oxidation and sarcoplasmic reticulum Ca2+ leak in cardiomyocytes: Role of adenine nucleotide translocase","volume":"1852","author":"Roussel","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12404","DOI":"10.1016\/S0021-9258(19)86329-9","article-title":"In vitro effects of palmitylcarnitine on cardiac plasma membrane Na,K-ATPase, and sarcoplasmic reticulum Ca2+-ATPase and Ca2+ transport","volume":"254","author":"Adams","year":"1979","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0014-5793(00)01817-2","article-title":"Regulation of the activity of caspases by L-carnitine and palmitoylcarnitine","volume":"478","author":"Mutomba","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/00005344-200007000-00002","article-title":"Long-chain acylcarnitine induces Ca2+ efflux from the sarcoplasmic reticulum","volume":"36","author":"Yamada","year":"2000","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1080\/14767058.2017.1319354","article-title":"Amino acid and acylcarnitine profiles in perinatal asphyxia: A case-control study","volume":"31","year":"2018","journal-title":"J. Matern. Fetal. Neonatal Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1161\/01.STR.0000198892.15269.f7","article-title":"Carnitine treatment inhibits increases in cerebral carnitine esters and glutamate detected by mass spectrometry after hypoxia-ischemia in newborn rats","volume":"37","author":"Wainwright","year":"2006","journal-title":"Stroke"},{"key":"ref_22","first-page":"817","article-title":"L-carnitine pre-treatment reduces apoptotic cell death in seven-day-old rats hypoxia ischemia","volume":"28","author":"Onal","year":"2010","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/jnc.14072","article-title":"Developmental regulation and localization of carnitine palmitoyltransferases (CPTs) in rat brain","volume":"142","author":"Jernberg","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e65400","DOI":"10.7554\/eLife.65400","article-title":"Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics","volume":"13","author":"Stokes","year":"2021","journal-title":"Elife"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5044","DOI":"10.1210\/jc.2016-1859","article-title":"Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans","volume":"101","author":"Xu","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fncel.2017.00078","article-title":"Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges","volume":"11","author":"Millar","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"F220","DOI":"10.1136\/adc.2008.148205","article-title":"Long-term outcome after neonatal hypoxic-ischaemic encephalopathy","volume":"95","author":"Jongmans","year":"2010","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"147370","DOI":"10.1016\/j.brainres.2021.147370","article-title":"Interaction of maternal immune activation and genetic interneuronal inhibition","volume":"1759","author":"Anderson","year":"2021","journal-title":"Brain Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1161\/CIRCULATIONAHA.115.019351","article-title":"Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension","volume":"133","author":"Brittain","year":"2016","journal-title":"Circulation"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/5\/467\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:16:33Z","timestamp":1760138193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/12\/5\/467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,22]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["metabo12050467"],"URL":"https:\/\/doi.org\/10.3390\/metabo12050467","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,22]]}}}