{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T18:14:38Z","timestamp":1762107278759,"version":"build-2065373602"},"reference-count":72,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-15-00454"],"award-info":[{"award-number":["22-15-00454"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxic\u2013ischemic encephalopathy (HIE) is a severe neurological disorder caused by perinatal asphyxia with significant consequences. Early recognition and intervention are crucial, with therapeutic hypothermia (TH) being the primary treatment, but its efficacy depends on early initiation of treatment. Accurately assessing the HIE severity in neonatal care poses challenges, but omics approaches have made significant contribution to understanding its complex pathophysiology. Our study further explores the impact of HIE on the blood metabolome over time and investigated changes associated with hypothermia\u2019s therapeutic effects. Using a rat model of hypoxic\u2013ischemic brain injury, we comprehensively analyzed dried blood spot samples for fat-soluble compounds using HPLC-MS. Our research shows significant changes in the blood metabolome after HIE, with a particularly rapid recovery of lipid metabolism observed. Significant changes in lipid metabolites were observed after 3 h of HIE, including increases in ceramides, carnitines, certain fatty acids, phosphocholines, and phosphoethanolamines, while sphingomyelins and N-acylethanolamines (NAEs) decreased (p &lt; 0.05). Furthermore, NAEs were found to be significant features in the OPLS-DA model for HIE diagnosis, with an area under the curve of 0.812. TH showed a notable association with decreased concentrations of ceramides. Enrichment analysis further corroborated these observations, showing modulation in several key metabolic pathways, including arachidonic acid oxylipin metabolism, eicosanoid metabolism via lipooxygenases, and leukotriene C4 synthesis deficiency. Our study reveals dynamic changes in the blood metabolome after HIE and the therapeutic effects of hypothermia, which improves our understanding of the pathophysiology of HIE and could lead to the development of new rapid diagnostic approaches for neonatal HIE.<\/jats:p>","DOI":"10.3390\/ijms25168903","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T06:23:20Z","timestamp":1723789400000},"page":"8903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dried Blood Spot Metabolome Features of Ischemic\u2013Hypoxic Encephalopathy: A Neonatal Rat Model"],"prefix":"10.3390","volume":"25","author":[{"given":"Chupalav","family":"Eldarov","sequence":"first","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Starodubtseva","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Shevtsova","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirill","family":"Goryunov","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg","family":"Ionov","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Frankevich","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"Laboratory of Translational Medicine, Siberian State Medical University, 634050 Tomsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2838-3704","authenticated-orcid":false,"given":"Egor","family":"Plotnikov","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gennady","family":"Sukhikh","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0863-8490","authenticated-orcid":false,"given":"Dmitry","family":"Zorov","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0581-9755","authenticated-orcid":false,"given":"Denis","family":"Silachev","sequence":"additional","affiliation":[{"name":"V.I. Kulakov National Medical Research Center for Obstetrics Gynecology and Perinatology, Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia"},{"name":"A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,15]]},"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":"224","DOI":"10.1016\/j.ejpn.2008.05.001","article-title":"A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy","volume":"13","author":"Pin","year":"2009","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s12519-023-00698-7","article-title":"Biomarkers of hypoxic-ischemic encephalopathy: A systematic review","volume":"19","author":"Caramelo","year":"2023","journal-title":"World J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJMoa0900854","article-title":"Moderate hypothermia to treat perinatal asphyxial encephalopathy","volume":"361","author":"Azzopardi","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Abate, B.B., Bimerew, M., Gebremichael, B., Mengesha Kassie, A., Kassaw, M., Gebremeskel, T., and Bayih, W.A. (2021). Effects of therapeutic hypothermia on death among asphyxiated neonates with hypoxic-ischemic encephalopathy: A systematic review and meta-analysis of randomized control trials. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247229"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sun, Y.J., Zhang, Z.Y., Fan, B., and Li, G.Y. (2019). Neuroprotection by Therapeutic Hypothermia. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00586"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.21037\/tp-23-253","article-title":"A narrative review on treatment strategies for neonatal hypoxic ischemic encephalopathy","volume":"12","author":"Korf","year":"2023","journal-title":"Transl. Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ovcjak, A., Pontello, R., Miller, S.P., Sun, H.S., and Feng, Z.P. (2023). Hypothermia combined with neuroprotective adjuvants shortens the duration of hospitalization in infants with hypoxic ischemic encephalopathy: Meta-analysis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1037131"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/pr.2016.198","article-title":"Therapeutic hypothermia translates from ancient history in to practice","volume":"81","author":"Gunn","year":"2017","journal-title":"Pediatr. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.17219\/acem\/124437","article-title":"Methods for assessing the severity of perinatal asphyxia and early prognostic tools in neonates with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia","volume":"29","author":"Walas","year":"2020","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"She, H.Q., Sun, Y.F., Chen, L., Xiao, Q.X., Luo, B.Y., Zhou, H.S., Zhou, D., Chang, Q.Y., and Xiong, L.L. (2023). Current analysis of hypoxic-ischemic encephalopathy research issues and future treatment modalities. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1136500"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Landucci, E., Pellegrini-Giampietro, D.E., and Facchinetti, F. (2022). Experimental Models for Testing the Efficacy of Pharmacological Treatments for Neonatal Hypoxic-Ischemic Encephalopathy. Biomedicines, 10.","DOI":"10.3390\/biomedicines10050937"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/17460441.2019.1573984","article-title":"Animal models of ischemic stroke and their impact on drug discovery","volume":"14","author":"Hermann","year":"2019","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Shevtsova, Y., Eldarov, C., Starodubtseva, N., Goryunov, K., Chagovets, V., Ionov, O., Plotnikov, E., and Silachev, D. (2023). Identification of Metabolomic Signatures for Ischemic Hypoxic Encephalopathy Using a Neonatal Rat Model. Children, 10.","DOI":"10.3390\/children10101693"},{"key":"ref_15","first-page":"5","article-title":"Recent Advances in Diagnostics of Neonatal Hypoxic Ischemic Encephalopathy","volume":"4","author":"Starodubtseva","year":"2022","journal-title":"Bull. Russ. State Med. Univ."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shevtsova, Y., Starodubtseva, N., Tokareva, A., Goryunov, K., Sadekova, A., Vedikhina, I., Ivanetz, T., Ionov, O., Frankevich, V., and Plotnikov, E. (2024). Metabolite Biomarkers for Early Ischemic\u2013Hypoxic Encephalopathy: An Experimental Study Using the NeoBase 2 MSMS Kit in a Rat Model. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042035"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.redox.2017.02.002","article-title":"Plasma metabolite score correlates with Hypoxia time in a newly born piglet model for asphyxia","volume":"12","author":"Kuligowski","year":"2017","journal-title":"Redox Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/s41372-018-0296-3","article-title":"The complexity of physicians\u2019 understanding and management of prognostic uncertainty in neonatal hypoxic-ischemic encephalopathy","volume":"39","author":"Rasmussen","year":"2019","journal-title":"J. Perinatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1053\/j.semperi.2016.11.008","article-title":"Challenges in neurologic prognostication after neonatal brain injury","volume":"41","author":"Natarajan","year":"2017","journal-title":"Semin. Perinatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e07411","DOI":"10.1016\/j.heliyon.2021.e07411","article-title":"Predictive modelling of hypoxic ischaemic encephalopathy risk following perinatal asphyxia","volume":"7","author":"Mooney","year":"2021","journal-title":"Heliyon"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.pedneo.2014.12.005","article-title":"Can We Predict Functional Outcome in Neonates with Hypoxic Ischemic Encephalopathy by the Combination of Neuroimaging and Electroencephalography?","volume":"56","author":"Nanavati","year":"2015","journal-title":"Pediatr. Neonatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1177\/0883073815573319","article-title":"An Evaluation of Cerebral and Systemic Predictors of 18-Month Outcomes for Neonates with Hypoxic Ischemic Encephalopathy","volume":"30","author":"Shellhaas","year":"2015","journal-title":"J. Child Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ejpn.2012.11.004","article-title":"Prediction of neurodevelopmental outcome in term neonates with hypoxic-ischemic encephalopathy","volume":"17","author":"Polat","year":"2013","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s11910-012-0254-y","article-title":"Neurodiagnostic techniques in neonatal critical care","volume":"12","author":"Chang","year":"2012","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wang, Z., Zhang, P., Zhou, W., Xia, S., Zhou, W., Zhou, X., Cheng, X., Shi, Y., Lin, Z., and Song, D. (2021). Neonatal hypoxic-ischemic encephalopathy diagnosis and treatment: A National Survey in China. BMC Pediatr., 21.","DOI":"10.1186\/s12887-021-02737-6"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fanos, V., Noto, A., Xanthos, T., Lussu, M., Murgia, F., Barberini, L., Finco, G., D\u2019Aloja, E., Papalois, A., and Iacovidou, N. (2014). Metabolomics network characterization of resuscitation after normocapnic hypoxia in a newborn piglet model supports the hypothesis that room air is better. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/731620"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/(SICI)1097-4547(19990115)55:2<158::AID-JNR3>3.0.CO;2-1","article-title":"Rat model of perinatal hypoxic-ischemic brain damage","volume":"55","author":"Vannucci","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000085978","article-title":"Perinatal hypoxic-ischemic brain damage: Evolution of an animal model","volume":"27","author":"Vannucci","year":"2005","journal-title":"Dev. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/pr.2014.70","article-title":"Metabolic adaptation and neuroprotection differ in the retina and choroid in a piglet model of acute postnatal hypoxia","volume":"76","author":"Arduini","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/pr.2013.88","article-title":"1H nuclear magnetic resonance brain metabolomics in neonatal mice after hypoxia-ischemia distinguished normothermic recovery from mild hypothermia recoveries","volume":"74","author":"Liu","year":"2013","journal-title":"Pediatr. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000523990","article-title":"The Vannucci Model of Hypoxic-Ischemic Injury in the Neonatal Rodent: 40 years Later","volume":"44","author":"Vannucci","year":"2022","journal-title":"Dev. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Rumajogee, P., Bregman, T., Miller, S.P., Yager, J.Y., and Fehlings, M.G. (2016). Rodent Hypoxia-Ischemia Models for Cerebral Palsy Research: A Systematic Review. Front. Neurol., 7.","DOI":"10.3389\/fneur.2016.00057"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1007\/s11306-014-0628-z","article-title":"The development and validation of a fast and robust dried blood spot based lipid profiling method to study infant metabolism","volume":"10","author":"Koulman","year":"2014","journal-title":"Metabolomics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/bdr2.1653","article-title":"Mandatory newborn screening in the United States: History, current status, and existential challenges","volume":"112","author":"McCandless","year":"2020","journal-title":"Birth Defects Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41431-018-0276-2","article-title":"Newborn dried blood spot samples in Denmark: The hidden figures of secondary use and research participation","volume":"27","author":"Nordfalk","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Solev\u00e5g, A.L., Zykova, S.N., Thorsby, P.M., and Schm\u00f6lzer, G.M. (2021). Metabolomics to Diagnose Oxidative Stress in Perinatal Asphyxia: Towards a Non-Invasive Approach. Antioxidants, 10.","DOI":"10.3390\/antiox10111753"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"238","DOI":"10.6065\/apem.2015.20.4.238","article-title":"Erratum to: Screening newborns for metabolic disorders based on targeted metabolomics using tandem mass spectrometry","volume":"20","author":"Yoon","year":"2015","journal-title":"Ann. Pediatr. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1159\/000467392","article-title":"Hypoxic-Ischaemic Encephalopathy and the Blood-Brain Barrier in Neonates","volume":"39","author":"Lee","year":"2017","journal-title":"Dev. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4230","DOI":"10.1021\/pr400617m","article-title":"1H NMR derived metabolomic profile of neonatal asphyxia in umbilical cord serum: Implications for hypoxic ischemic encephalopathy","volume":"12","author":"Reinke","year":"2013","journal-title":"J. Proteome Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/pr.2016.66","article-title":"Changes of the plasma metabolome of newly born piglets subjected to postnatal hypoxia and resuscitation with air","volume":"80","author":"Solberg","year":"2016","journal-title":"Pediatr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"389","DOI":"10.55782\/ane-2008-1705","article-title":"CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia","volume":"68","author":"Fiedorowicz","year":"2008","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1123\/ijsnem.18.2.191","article-title":"Choline: An important micronutrient for maximal endurance-exercise performance?","volume":"18","author":"Penry","year":"2008","journal-title":"Int. J. Sport Nutr. Exerc. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s13760-020-01308-3","article-title":"Pathophysiology of hypoxic-ischemic encephalopathy: A review of the past and a view on the future","volume":"120","author":"Greco","year":"2020","journal-title":"Acta Neurol. Belg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1089\/ars.2010.3474","article-title":"Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke","volume":"14","author":"Rink","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"560","DOI":"10.5483\/BMBRep.2008.41.8.560","article-title":"Phospholipase A2, reactive oxygen species, and lipid peroxidation in CNS pathologies","volume":"41","author":"Adibhatla","year":"2008","journal-title":"BMB Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF03159946","article-title":"Changes of Polyphosphoinositides, Lysophospholipid, and Free Fatty Acids in Transient Cerebral Ischemia of Rat Brain","volume":"12","author":"Kinouchi","year":"1990","journal-title":"Mol. Chem. Neuropathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/(SICI)1098-1136(200003)30:1<92::AID-GLIA10>3.0.CO;2-W","article-title":"Lysophosphatidylcholine Induces Rapid Recruitment and Activation of Macrophages in the Adult Mouse Spinal Cord","volume":"30","author":"Ousman","year":"2000","journal-title":"Glia"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1113\/jphysiol.2004.060632","article-title":"Physiological mechanisms of lysophosphatidylcholine-induced de-ramification of murine microglia","volume":"557","author":"Schilling","year":"2004","journal-title":"J. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1161\/01.STR.0000126044.83777.f4","article-title":"Reperfusion-induced oxidative\/nitrative injury to neurovascular unit after focal cerebral ischemia","volume":"35","author":"Can","year":"2004","journal-title":"Stroke"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/j.1471-4159.2006.04371.x","article-title":"Modulation of inflammation in brain: A matter of fat","volume":"101","author":"Farooqui","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.freeradbiomed.2005.08.044","article-title":"Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia","volume":"40","author":"Hatcher","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.plefa.2014.05.007","article-title":"\u03b2-oxidation and rapid metabolism, but not uptake regulate brain eicosapentaenoic acid levels","volume":"92","author":"Chen","year":"2015","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"18901","DOI":"10.1073\/pnas.0809765105","article-title":"Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways","volume":"105","author":"Inceoglu","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1124\/jpet.111.180505","article-title":"Epoxyeicosatrienoic acids attenuate reactive oxygen species level, mitochondrial dysfunction, caspase activation, and apoptosis in carcinoma cells treated with arsenic trioxide","volume":"339","author":"Liu","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Solberg, R., Enot, D., Deigner, H.P., Koal, T., Scholl-B\u00fcrgi, S., Saugstad, O.D., and Keller, M. (2010). Metabolomic analyses of plasma reveals new insights into asphyxia and resuscitation in pigs. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009606"},{"key":"ref_56","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_57","first-page":"S89","article-title":"Hypoxia-induced lipid peroxidation in the brain during postnatal ontogenesis","volume":"61","year":"2012","journal-title":"Physiol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1046\/j.1471-4159.2003.02244.x","article-title":"Massive accumulation of N-acylethanolamines after stroke. Cell signalling in acute cerebral ischemia?","volume":"88","author":"Berger","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.phrs.2014.05.009","article-title":"Roles of fatty acid ethanolamides (FAE) in traumatic and ischemic brain injury","volume":"86","author":"Esposito","year":"2014","journal-title":"Pharmacol. Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Kasatkina, L.A., Heinemann, A., Hudz, Y.A., Thomas, D., and Sturm, E.M. (2020). Stearoylethanolamide interferes with retrograde endocannabinoid signalling and supports the blood-brain barrier integrity under acute systemic inflammation. Biochem. Pharmacol., 174.","DOI":"10.1016\/j.bcp.2019.113783"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00018-012-1038-x","article-title":"Ceramide function in the brain: When a slight tilt is enough","volume":"70","author":"Mencarelli","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"295","DOI":"10.5604\/17322693.999024","article-title":"[The role of ceramides in selected brain pathologies: Ischemia\/hypoxia, Alzheimer disease]","volume":"66","author":"Car","year":"2012","journal-title":"Postep. Hig. Med. Dosw."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Pant, D.C., Aguilera-Albesa, S., and Pujol, A. (2020). Ceramide signalling in inherited and multifactorial brain metabolic diseases. Neurobiol. Dis., 143.","DOI":"10.1016\/j.nbd.2020.105014"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jfma.2021.01.006","article-title":"Plasma ceramides are associated with outcomes in acute ischemic stroke patients","volume":"121","author":"Lee","year":"2022","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1021\/acs.jproteome.9b00370","article-title":"Sphingolipidomics Investigation of the Temporal Dynamics after Ischemic Brain Injury","volume":"18","author":"Chao","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jfma.2022.08.021","article-title":"Investigating sphingolipids as biomarkers for the outcomes of acute ischemic stroke patients receiving endovascular treatment","volume":"122","author":"Lee","year":"2023","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1542\/peds.102.5.1098","article-title":"Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep","volume":"102","author":"Gunn","year":"1998","journal-title":"Pediatrics"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/pch\/pxy028","article-title":"Hypothermia for newborns with hypoxic-ischemic encephalopathy","volume":"23","author":"Lemyre","year":"2018","journal-title":"Paediatr. Child Health"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.cca.2015.02.004","article-title":"Proton nuclear magnetic resonance spectroscopy of urine samples in preterm asphyctic newborn: A metabolomic approach","volume":"444","author":"Longini","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/B978-0-444-64029-1.00013-8","article-title":"Biomarkers in neonatal hypoxic-ischemic encephalopathy-Review of the literature to date and future directions for research","volume":"162","author":"Murray","year":"2019","journal-title":"Handb. Clin. Neurol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1750-3639.2005.tb00526.x","article-title":"Excitotoxicity in perinatal brain injury","volume":"15","author":"Johnston","year":"2005","journal-title":"Brain Pathol."},{"key":"ref_72","first-page":"762","article-title":"Hypoxanthine: A marker for asphyxia","volume":"72","author":"Pietz","year":"1988","journal-title":"Obstet. Gynecol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8903\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:37:18Z","timestamp":1760110638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8903"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,15]]},"references-count":72,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168903"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168903","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,8,15]]}}}