{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:16:38Z","timestamp":1790738198515,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2019R1A6A1A11036849"],"award-info":[{"award-number":["NRF-2019R1A6A1A11036849"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2022R1F1A1065996"],"award-info":[{"award-number":["NRF-2022R1F1A1065996"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2020R1F1A1071973"],"award-info":[{"award-number":["NRF-2020R1F1A1071973"]}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2019R1A6A1A11036849"],"award-info":[{"award-number":["NRF-2019R1A6A1A11036849"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2022R1F1A1065996"],"award-info":[{"award-number":["NRF-2022R1F1A1065996"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2020R1F1A1071973"],"award-info":[{"award-number":["NRF-2020R1F1A1071973"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Research reports using animal models of ischemic insults have demonstrated that oxcarbazepine (a carbamazepine analog: one of the anticonvulsant compounds) extends neuroprotective effects against cerebral or forebrain injury induced by ischemia and reperfusion. However, research on protective effects against ischemia and reperfusion cerebellar injury induced by cardiac arrest (CA) and the return of spontaneous circulation has been poor. Rats were assigned to four groups as follows: (Groups 1 and 2) sham asphyxial CA and vehicle- or oxcarbazepine-treated, and (Groups 3 and 4) CA and vehicle- or oxcarbazepine-treated. Vehicle (0.3% dimethyl sulfoxide\/saline) or oxcarbazepine (200 mg\/kg) was administered intravenously ten minutes after the return of spontaneous circulation. In this study, CA was induced by asphyxia using vecuronium bromide (2 mg\/kg). We conducted immunohistochemistry for calbindin D-28kDa and Fluoro-Jade B histofluorescence to examine Purkinje cell death induced by CA. In addition, immunohistochemistry for 4-hydroxy-2-nonenal (4HNE) was carried out to investigate CA-induced oxidative stress, and immunohistochemistry for Cu, Zn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) was performed to examine changes in endogenous antioxidant enzymes. Oxcarbazepine treatment after CA significantly increased the survival rate and improved neurological deficit when compared with vehicle-treated rats with CA (survival rates \u2265 63.6 versus 6.5%), showing that oxcarbazepine treatment dramatically protected cerebellar Purkinje cells from ischemia and reperfusion injury induced by CA. The salvation of the Purkinje cells from ischemic injury by oxcarbazepine treatment paralleled a dramatic reduction in 4HNE (an end-product of lipid peroxidation) and increased or maintained the endogenous antioxidant enzymes (SOD1 and SOD2). In brief, this study shows that therapeutic treatment with oxcarbazepine after CA apparently saved cerebellar neurons (Purkinje cells) from CA-induced neuronal death by attenuating oxidative stress and suggests that oxcarbazepine can be utilized as a therapeutic medicine for ischemia and reperfusion brain (cerebellar) injury induced by CA.<\/jats:p>","DOI":"10.3390\/antiox11122450","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T02:59:01Z","timestamp":1670900341000},"page":"2450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Therapeutic Administration of Oxcarbazepine Saves Cerebellar Purkinje Cells from Ischemia and Reperfusion Injury Induced by Cardiac Arrest through Attenuation of Oxidative Stress"],"prefix":"10.3390","volume":"11","author":[{"given":"Yang Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Surgery, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Kyeong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-4508","authenticated-orcid":false,"given":"Dae Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University, Gangneung, Gangwon 25457, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongkweon","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Hwi","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myoung Cheol","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24289, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7178-6501","authenticated-orcid":false,"given":"Moo-Ho","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0314-5195","authenticated-orcid":false,"given":"Il Jun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Hallym University, Chuncheon, Gangwon 24252, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1176\/jnp.2009.21.3.245","article-title":"Evaluating the affective component of the cerebellar cognitive affective syndrome","volume":"21","author":"Wolf","year":"2009","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.conb.2006.08.016","article-title":"Learning to predict the future: The cerebellum adapts feedforward movement control","volume":"16","author":"Bastian","year":"2006","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1055\/s-2002-36759","article-title":"The history of the development of the cerebellar examination","volume":"22","author":"Fine","year":"2002","journal-title":"Semin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.resuscitation.2012.05.022","article-title":"Cerebellar purkinje cell neurodegeneration after cardiac arrest: Effect of therapeutic hypothermia","volume":"83","author":"Paine","year":"2012","journal-title":"Resuscitation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3511","DOI":"10.1097\/00003246-200010000-00027","article-title":"Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats","volume":"28","author":"Hickey","year":"2000","journal-title":"Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1161\/01.STR.0000217303.22856.38","article-title":"Multiple mechanisms underlying the neuroprotective effects of antiepileptic drugs against in vitro ischemia","volume":"37","author":"Costa","year":"2006","journal-title":"Stroke"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1097\/TA.0000000000001612","article-title":"Valproic acid decreases brain lesion size and improves neurologic recovery in swine subjected to traumatic brain injury, hemorrhagic shock, and polytrauma","volume":"83","author":"Nikolian","year":"2017","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.spinee.2016.04.013","article-title":"Combining neuroprotective agents: Effect of riluzole and magnesium in a rat model of thoracic spinal cord injury","volume":"16","author":"Vasconcelos","year":"2016","journal-title":"Spine J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/ana.10603","article-title":"Antiepileptic drugs as a possible neuroprotective strategy in brain ischemia","volume":"53","author":"Calabresi","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_10","first-page":"598493","article-title":"Modulation of antioxidant enzymatic activities by certain antiepileptic drugs (valproic acid, oxcarbazepine, and topiramate): Evidence in humans and experimental models","volume":"2013","author":"Sampieri","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_11","first-page":"319","article-title":"Comparative assays of antiepileptic drugs in mice and rats","volume":"106","author":"Swinyard","year":"1952","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1023\/A:1014814924965","article-title":"Mechanisms of action of carbamazepine and its derivatives, oxcarbazepine, bia 2-093, and bia 2-024","volume":"27","author":"Ambrosio","year":"2002","journal-title":"Neurochem. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/BF01345257","article-title":"The importance of voltage-dependent sodium channels in cerebral ischaemia","volume":"14","author":"Carter","year":"1998","journal-title":"Amino Acids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1097\/00001756-200107200-00042","article-title":"Lamotrigine inhibition of glutamate release from isolated cerebrocortical nerve terminals (synaptosomes) by suppression of voltage-activated calcium channel activity","volume":"12","author":"Wang","year":"2001","journal-title":"Neuroreport"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109850","DOI":"10.1016\/j.biopha.2020.109850","article-title":"Post-treatment with oxcarbazepine confers potent neuroprotection against transient global cerebral ischemic injury by activating nrf2 defense pathway","volume":"124","author":"Park","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s11886-004-0009-8","article-title":"Mechanisms of ischemic brain injury","volume":"6","author":"Janardhan","year":"2004","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s10072-017-2938-1","article-title":"Pathogenic mechanisms following ischemic stroke","volume":"38","author":"Khoshnam","year":"2017","journal-title":"Neurol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0168-0102(01)00282-6","article-title":"Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils","volume":"41","author":"Mhadu","year":"2001","journal-title":"Neurosci. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1742-2094-9-69","article-title":"Inhibition of p2x7 receptor ameliorates transient global cerebral ischemia\/reperfusion injury via modulating inflammatory responses in the rat hippocampus","volume":"9","author":"Chu","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9790","DOI":"10.1002\/jcb.27297","article-title":"Comparison between the effect of human wharton\u2019s jelly-derived mesenchymal stem cells and levetiracetam on brain infarcts in rats","volume":"119","author":"Hussein","year":"2018","journal-title":"J. Cell Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1007\/s11064-016-1951-8","article-title":"Increases of catalase and glutathione peroxidase expressions by lacosamide pretreatment contributes to neuroprotection against experimentally induced transient cerebral ischemia","volume":"41","author":"Choi","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejphar.2013.03.020","article-title":"Valproic acid attenuates ischemia-reperfusion injury in the rat brain through inhibition of oxidative stress and inflammation","volume":"707","author":"Suda","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.resuscitation.2014.03.314","article-title":"Global and regional differences in cerebral blood flow after asphyxial versus ventricular fibrillation cardiac arrest in rats using asl-mri","volume":"85","author":"Drabek","year":"2014","journal-title":"Resuscitation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.resuscitation.2009.09.018","article-title":"A rodent model of emergency cardiopulmonary bypass resuscitation with different temperatures after asphyxial cardiac arrest","volume":"81","author":"Han","year":"2010","journal-title":"Resuscitation"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kim, J., Yin, T., Yin, M., Zhang, W., Shinozaki, K., Selak, M.A., Pappan, K.L., Lampe, J.W., and Becker, L.B. (2014). Examination of physiological function and biochemical disorders in a rat model of prolonged asphyxia-induced cardiac arrest followed by cardio pulmonary bypass resuscitation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112012"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1097\/CCM.0b013e318212020a","article-title":"Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest","volume":"39","author":"Che","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0300-9572(96)01055-6","article-title":"Utstein-style guidelines for uniform reporting of laboratory cpr research. A statement for healthcare professionals from a task force of the american heart association, the american college of emergency physicians, the american college of cardiology, the european resuscitation council, the heart and stroke foundation of canada, the institute of critical care medicine, the safar center for resuscitation research, and the society for academic emergency medicine","volume":"33","author":"Idris","year":"1996","journal-title":"Resuscitation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1161\/01.STR.29.6.1229","article-title":"A reproducible model of circulatory arrest and remote resuscitation in rats for nmr investigation","volume":"29","author":"Liachenko","year":"1998","journal-title":"Stroke J. Cereb. Circ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s10571-009-9465-4","article-title":"Calcium binding proteins immunoreactivity in the rat basolateral amygdala following myocardial infarction","volume":"30","author":"Lee","year":"2010","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/0306-4522(91)90001-5","article-title":"Selective vulnerability of the hippocampus in brain ischemia","volume":"40","author":"Freund","year":"1991","journal-title":"Neuroscience"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1111\/j.1471-4159.1987.tb01001.x","article-title":"Altered mitochondrial respiration in selectively vulnerable brain subregions following transient forebrain ischemia in the rat","volume":"49","author":"Sims","year":"1987","journal-title":"J. Neurochem."},{"key":"ref_32","first-page":"331","article-title":"Why do purkinje cells die so easily after global brain ischemia? Aldolase c, eaat4, and the cerebellar contribution to posthypoxic myoclonus","volume":"89","author":"Welsh","year":"2002","journal-title":"Adv. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0079-6123(08)61973-1","article-title":"Selective neuronal vulnerability: Morphological and molecular characteristics","volume":"63","author":"Pulsinelli","year":"1985","journal-title":"Prog. Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/0959-4388(93)90168-X","article-title":"On the cerebellum and motor learning","volume":"3","author":"Llinas","year":"1993","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S1364-6613(98)01210-8","article-title":"The anatomy of the cerebellum","volume":"2","author":"Voogd","year":"1998","journal-title":"Trends Cogn. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ncl.2005.11.001","article-title":"Movement disorders after resuscitation from cardiac arrest","volume":"24","author":"Venkatesan","year":"2006","journal-title":"Neurol. Clin."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/jcbfm.1995.129","article-title":"Outcome model of asphyxial cardiac arrest in rats","volume":"15","author":"Katz","year":"1995","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112983","DOI":"10.1016\/j.expneurol.2019.112983","article-title":"Melatonin alleviates asphyxial cardiac arrest-induced cerebellar purkinje cell death by attenuation of oxidative stress","volume":"320","author":"Cho","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ahn, J.H., Shin, B.N., Park, J.H., Lee, T.K., Park, Y.E., Lee, J.C., Yang, G.E., Shin, M.C., Cho, J.H., and Lee, K.C. (2019). Pre- and post-treatment with novel antiepileptic drug oxcarbazepine exerts neuroprotective effect in the hippocampus in a gerbil model of transient global cerebral ischemia. Brain Sci., 9.","DOI":"10.3390\/brainsci9100279"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12035-012-8344-z","article-title":"Molecular mechanisms of ischemia-reperfusion injury in brain: Pivotal role of the mitochondrial membrane potential in reactive oxygen species generation","volume":"47","author":"Sanderson","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1747-4949.2009.00387.x","article-title":"Oxidative stress and its role in the pathogenesis of ischaemic stroke","volume":"4","author":"Allen","year":"2009","journal-title":"Int. J. Stroke"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1177\/0003319713506516","article-title":"Link between oxidative stress and acute brain ischemia","volume":"65","author":"Radak","year":"2014","journal-title":"Angiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1089\/152308603770310266","article-title":"Reactive oxygen radicals and pathogenesis of neuronal death after cerebral ischemia","volume":"5","author":"Sugawara","year":"2003","journal-title":"Antioxid. Redox Signal"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/00004647-200101000-00002","article-title":"Reactive oxygen radicals in signaling and damage in the ischemic brain","volume":"21","author":"Chan","year":"2001","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yang, G.E., Tae, H.J., Lee, T.K., Park, Y.E., Cho, J.H., Kim, D.W., Park, J.H., Ahn, J.H., Ryoo, S., and Kim, Y.M. (2019). Risperidone treatment after transient ischemia induces hypothermia and provides neuroprotection in the gerbil hippocampus by decreasing oxidative stress. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184621"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"149","DOI":"10.5115\/acb.2014.47.3.149","article-title":"Neuroprotection of antioxidant enzymes against transient global cerebral ischemia in gerbils","volume":"47","author":"Lee","year":"2014","journal-title":"Anat. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"872","DOI":"10.3389\/fpls.2018.00872","article-title":"Copper nanoparticles induced genotoxicty, oxidative stress, and changes in superoxide dismutase (sod) gene expression in cucumber (Cucumis sativus) plants","volume":"9","author":"Mosa","year":"2018","journal-title":"Front. Plant Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6897","DOI":"10.1007\/s11033-021-06692-4","article-title":"Cloning of mn-sod gene and its mrna expression difference and antioxidant enzyme activities under hypoxia stress of cobia rachycentron canadum","volume":"48","author":"Zhang","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.bbadis.2009.09.002","article-title":"Mitochondrial and apoptotic neuronal death signaling pathways in cerebral ischemia","volume":"1802","author":"Niizuma","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1097\/00002727-200310000-00003","article-title":"Pharmacological treatment of acute ischemic stroke","volume":"26","author":"Murphy","year":"2003","journal-title":"Crit. Care Nurs. Q."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ahn, J.H., Shin, M.C., Kim, D.W., Kim, H., Song, M., Lee, T.K., Lee, J.C., Kim, H., Cho, J.H., and Kim, Y.M. (2019). Antioxidant properties of fucoidan alleviate acceleration and exacerbation of hippocampal neuronal death following transient global cerebral ischemia in high-fat diet-induced obese gerbils. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030554"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/12\/2450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:39:57Z","timestamp":1760146797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/12\/2450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,12]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["antiox11122450"],"URL":"https:\/\/doi.org\/10.3390\/antiox11122450","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,12]]}}}