{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T01:46:23Z","timestamp":1785807983809,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS125775"],"award-info":[{"award-number":["R01NS125775"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS091616"],"award-info":[{"award-number":["R01NS091616"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R21NS106949"],"award-info":[{"award-number":["R21NS106949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["535 T34GM146637"],"award-info":[{"award-number":["535 T34GM146637"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R25GM119975"],"award-info":[{"award-number":["R25GM119975"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Ischemic stroke is a major cause of long-term disability and death, with oxidative stress contributing substantially to post-ischemic injury. Reperfusion restores oxygen supply but simultaneously increases reactive oxygen species (ROS), amplifying secondary neuronal damage. This study examined time-dependent changes in systemic thiol redox status following transient middle cerebral artery occlusion (tMCAO) in rats. Plasma concentrations of cysteine (CySH), cystine (CySS), glutathione (GSH), and glutathione disulfide (GSSG), along with corresponding CySS\/CySH and GSSG\/GSH ratios and redox potentials (Eh), were evaluated 24 and 48 h after occlusion. At 24 h, thiol concentrations and redox ratios showed no significant differences between sham and tMCAO groups. By 48 h, a marked oxidative shift emerged, characterized by reduced CySH, elevated GSSG, and significant increases in both CySS\/CySH and GSSG\/GSH ratios. Redox potentials also demonstrated substantial oxidation at this time point. These findings indicate that prolonged ischemia\u2013reperfusion induces systemic oxidative stress, with plasma redox status serving as a sensitive indicator of reperfusion-related injury. The results underscore the plasma redox status as a potentially sensitive biomarker of reperfusion-induced oxidative injury and support the therapeutic value of targeting redox imbalance to mitigate oxidative damage following stroke.<\/jats:p>","DOI":"10.3390\/antiox15010117","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:27:53Z","timestamp":1768570073000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Redox State of Glutathione and Cysteine in Plasma Following Acute Stroke"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2533-1068","authenticated-orcid":false,"given":"Christopher","family":"McGinley","sequence":"first","affiliation":[{"name":"Department of Anatomy, Howard University College of Medicine, 520 W. Street NW, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1768-1653","authenticated-orcid":false,"given":"Oyinkansola","family":"Adeyemi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Howard University College of Medicine, 520 W. Street NW, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6817-3269","authenticated-orcid":false,"given":"Oluwafayokemi","family":"Oyolola","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Howard University College of Medicine, 520 W. Street NW, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6636-1461","authenticated-orcid":false,"given":"Byron D.","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Howard University College of Medicine, 520 W. Street NW, Washington, DC 20059, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1725-6379","authenticated-orcid":false,"given":"Gregory D.","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Howard University College of Medicine, 520 W. Street NW, Washington, DC 20059, USA"},{"name":"Department of Natural Sciences, Southern University at New Orleans, 6400 Press Drive, New Orleans, LA 70126, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0166-2236(99)01401-0","article-title":"Pathobiology of ischemic stroke: An integrated view","volume":"22","author":"Dirnagl","year":"1999","journal-title":"Trends Neurosci."},{"key":"ref_2","first-page":"213","article-title":"Ischemia-reperfusion Injury in the Brain: Mechanisms and Potential Therapeutic Strategies","volume":"5","author":"Lin","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1750-3639.2000.tb00247.x","article-title":"Inflammation and stroke: Putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia","volume":"10","author":"Ginis","year":"2000","journal-title":"Brain Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.neuron.2010.07.002","article-title":"The science of stroke: Mechanisms in search of treatments","volume":"67","author":"Moskowitz","year":"2010","journal-title":"Neuron"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1016\/j.bbagen.2012.09.008","article-title":"Glutathione synthesis","volume":"1830","author":"Lu","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.freeradbiomed.2019.07.031","article-title":"Plasma cysteine\/cystine and glutathione\/glutathione disulfide redox potentials in HIV and COPD patients","volume":"143","author":"Watson","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1080\/13813450701661198","article-title":"The central role of glutathione in the pathophysiology of human diseases","volume":"113","author":"Franco","year":"2007","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrn1106","article-title":"Mechanisms, challenges, and opportunities in stroke","volume":"4","author":"Lo","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"26512","DOI":"10.1074\/jbc.R113.464131","article-title":"The redox proteome","volume":"288","author":"Go","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0006-2952(02)01172-3","article-title":"Cellular glutathione and thiols metabolism","volume":"64","author":"Dickinson","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1038\/s41589-019-0408-1","article-title":"The chemical basis of ferroptosis","volume":"15","author":"Conrad","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2020","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/ars.2017.7115","article-title":"GPx4, lipid peroxidation, and cell death: Discoveries, rediscoveries, and open issues","volume":"29","author":"Maiorino","year":"2018","journal-title":"Antioxid. Redox Signal"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.bbrc.2004.07.149","article-title":"Neuregulin-1 is neuroprotective and attenuates inflammatory responses induced by ischemic stroke","volume":"322","author":"Xu","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Surles-Zeigler, M.C., Li, Y., Distel, T.J., Omotayo, H., Ge, S., and Ford, B.D. (2018). Transcriptomic analysis of neuregulin-1 regulated genes following ischemic stroke by computational identification of promoter binding sites: A role for the ETS-1 transcription factor. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0197092"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.taap.2011.03.026","article-title":"Spatiotemporal pattern of neuronal injury induced by DFP in rats: A model for delayed neuronal cell death following acute OP intoxication","volume":"253","author":"Li","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7863412","DOI":"10.1155\/2018\/7863412","article-title":"Detection of HIV-1 and Human Proteins in Urinary Extracellular Vesicles from HIV+ Patients","volume":"2018","author":"Anyanwu","year":"2018","journal-title":"Adv. Virol."},{"key":"ref_18","first-page":"471","article-title":"Cysteine\/cystine redox signaling in cardiovascular disease","volume":"48","author":"Reed","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.freeradbiomed.2014.11.013","article-title":"The basics of thiols and cysteines in redox biology and chemistry","volume":"80","author":"Poole","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1042\/CS20180157","article-title":"Implications of plasma thiol redox in disease","volume":"132","author":"Go","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102780","DOI":"10.1016\/j.jbc.2022.102780","article-title":"Oxidative stress in the mitochondrial matrix underlies ischemia\/reperfusion-induced mitochondrial instability","volume":"299","author":"Solhjoo","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Arrivi, A., Barill\u00e0, F., Carnevale, R., Sordi, M., Pucci, G., Tanzilli, G., and Mangieri, E. (2022). Protective biomolecular mechanisms of glutathione sodium salt in ischemia-reperfusion injury in patients with acute coronary syndrome. Cells, 11.","DOI":"10.3390\/cells11243964"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1146\/annurev.bi.52.070183.003431","article-title":"Glutathione","volume":"52","author":"Meister","year":"1983","journal-title":"Annu. Rev. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mam.2008.08.006","article-title":"Glutathione: Overview of its protective roles, measurement, and biosynthesis","volume":"30","author":"Forman","year":"2009","journal-title":"Mol. Asp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF01870891","article-title":"Role of membrane transport in metabolism and function of glutathione in mammals","volume":"89","author":"Bannai","year":"1986","journal-title":"J. Membr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.niox.2018.05.005","article-title":"Cystine\/glutamate transporter, system xc-, is involved in nitric oxide production in mouse peritoneal macrophages","volume":"78","author":"Kobayashi","year":"2018","journal-title":"Nitric Oxide"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.redox.2016.12.035","article-title":"Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress","volume":"11","author":"Sies","year":"2017","journal-title":"Redox Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1089\/ars.2006.8.1865","article-title":"Redefining oxidative stress","volume":"8","author":"Jones","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.freeradbiomed.2008.05.004","article-title":"Thiol chemistry and specificity in redox signaling","volume":"45","author":"Winterbourn","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4403","DOI":"10.1074\/jbc.R111.283432","article-title":"Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides","volume":"287","author":"Rhee","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/S0891-5849(99)00176-8","article-title":"Biologic and pharmacologic regulation of mammalian glutathione synthesis","volume":"27","author":"Griffith","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00726-008-0202-y","article-title":"Cysteine dioxygenase: A robust system for regulation of cellular cysteine levels","volume":"37","author":"Stipanuk","year":"2009","journal-title":"Amino Acids"},{"key":"ref_33","first-page":"1228","article-title":"Regulatory phenomena in the glutathione peroxidase superfamily","volume":"9","year":"2020","journal-title":"Antioxidants"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/1\/117\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T12:58:44Z","timestamp":1769432324000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/1\/117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["antiox15010117"],"URL":"https:\/\/doi.org\/10.3390\/antiox15010117","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}