{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T15:54:12Z","timestamp":1783785252100,"version":"3.55.0"},"reference-count":51,"publisher":"IOP Publishing","issue":"2","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/page\/copyright"},{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior \u2013 Brasil","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"name":"FAEPEX","award":["2633\/17"],"award-info":[{"award-number":["2633\/17"]}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"crossref","award":["#2023\/06143-0"],"award-info":[{"award-number":["#2023\/06143-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Nanotechnology"],"published-print":{"date-parts":[[2025,1,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Reduced graphene oxide (rGO) has unique physicochemical properties that make it suitable for therapeutic applications in neurodegenerative scenarios. This study investigates the therapeutic potential of rGO in a cuprizone-induced demyelination model in mice through histomorphological techniques and analysis of biochemical parameters. We demonstrate that daily intraperitoneal administration of rGO (1 mg ml<jats:sup>\u22121<\/jats:sup>) for 21 days tends to reduce demyelination in the <jats:italic>Corpus callosum<\/jats:italic> by decreasing glial cell recruitment during the repair mechanism. Additionally, rGO interferes with oxidative stress markers in the brain and liver indicating potential neuroprotective effects in the central nervous system. No significant damage to vital organs was observed, suggesting that multiple doses could be used safely. However, further long-term investigations are needed to understand rGO distribution, metabolism, routes of action and associated challenges in central neurodegenerative therapies. Overall, these findings contribute to the comprehension of rGO effects <jats:italic>in vivo<\/jats:italic>, paving the way for possible future clinical research.<\/jats:p>","DOI":"10.1088\/1361-6528\/ad857e","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T22:48:50Z","timestamp":1728600530000},"page":"025102","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The therapeutic potential of reduced graphene oxide in attenuating cuprizone-induced demyelination in mice"],"prefix":"10.1088","volume":"36","author":[{"given":"Cintia","family":"Rizoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3477-3795","authenticated-orcid":false,"given":"Nathalia Medina","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8877-3160","authenticated-orcid":true,"given":"M\u00e1rio Roberto","family":"Mar\u00f3stica J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4113-0189","authenticated-orcid":false,"given":"Maria Alice","family":"da Cruz-H\u00f6fling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-2150","authenticated-orcid":false,"given":"Monique Culturato Padilha","family":"Mendon\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0812-1491","authenticated-orcid":true,"given":"Marcelo Bispo","family":"de Jesus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"nanoad857ebib1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S0076-6879(84)05016-3","article-title":"Catalase in vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzymol."},{"key":"nanoad857ebib2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ma15082898","article-title":"Biological responses in the blood and organs of rats to intraperitoneal inoculation of graphene and graphene oxide","volume":"15","author":"Aguado-Henche","year":"2022","journal-title":"Materials"},{"key":"nanoad857ebib3","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.carbon.2013.09.015","article-title":"Accelerated differentiation of neural stem cells into neurons on ginseng-reduced graphene oxide sheets","volume":"66","author":"Akhavan","year":"2014","journal-title":"Carbon"},{"key":"nanoad857ebib4","doi-asserted-by":"publisher","first-page":"5010","DOI":"10.3390\/ijms22095010","article-title":"Glutathione in the brain","volume":"22","author":"Aoyama","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"nanoad857ebib5","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1055\/s-0036-1579693","article-title":"Epidemiology of multiple sclerosis: from risk factors to prevention\u2013an update","volume":"36","author":"Ascherio","year":"2016","journal-title":"Semin. Neurol."},{"key":"nanoad857ebib6","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.jff.2013.11.011","article-title":"Intake of jaboticaba peel attenuates oxidative stress in tissues and reduces circulating saturated lipids of rats with high-fat diet-induced obesity","volume":"6","author":"Batista","year":"2014","journal-title":"J. Funct. Foods"},{"key":"nanoad857ebib7","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.cj.2017.04.003","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"nanoad857ebib8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11910-020-01046-2","article-title":"Impact of age on multiple sclerosis disease activity and progression","volume":"20","author":"Burcu","year":"2020","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"nanoad857ebib9","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/978-1-4939-6788-9_15","article-title":"Staining methods for normal and regenerative myelin in the nervous system","volume":"1560","author":"Carriel","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"nanoad857ebib10","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.biomaterials.2018.11.024","article-title":"Myelinated axons and functional blood vessels populate mechanically compliant RGO foams in chronic cervical hemisected rats","volume":"192","author":"Dom\u00ednguez-Bajo","year":"2019","journal-title":"Biomaterials"},{"key":"nanoad857ebib11","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"Ellman","year":"1959","journal-title":"Arch. Biochem. Biophys."},{"key":"nanoad857ebib12","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.yrtph.2015.11.015","article-title":"A review of toxicity studies of single-walled carbon nanotubes in laboratory animals","volume":"74","author":"Ema","year":"2016","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"nanoad857ebib13","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.yrtph.2017.01.011","article-title":"A review of toxicity studies on graphene-based nanomaterials in laboratory animals","volume":"85","author":"Ema","year":"2017","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"nanoad857ebib14","doi-asserted-by":"publisher","first-page":"10593","DOI":"10.1039\/d0tb00779j","article-title":"Reduced graphene oxide-GelMA-PCL hybrid nanofibers for peripheral nerve regeneration","volume":"8","author":"Fang","year":"2020","journal-title":"J. Mat. Chem. B"},{"key":"nanoad857ebib15","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.3390\/pharmaceutics15102441","article-title":"Strategies for drug delivery into the brain: a review on adenosine receptors modulation for central nervous system diseases therapy","volume":"15","author":"Fernandez","year":"2023","journal-title":"Pharmaceutics"},{"key":"nanoad857ebib16","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1259\/bjr\/21946513","article-title":"The corpus callosum: white matter or terra incognita","volume":"84","author":"Fitsiori","year":"2011","journal-title":"Br. J. Radiol."},{"key":"nanoad857ebib17","doi-asserted-by":"publisher","first-page":"945","DOI":"10.3390\/cells9040945","article-title":"Delayed demyelination and impaired remyelination in aged mice in the cuprizone model","volume":"9","author":"Gingele","year":"2020","journal-title":"Cells"},{"key":"nanoad857ebib18","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1242\/dmm.030205","article-title":"Neurodegenerative disease: models, mechanisms, and a new hope","volume":"10","author":"Gitler","year":"2017","journal-title":"DMM Dis. Models Mech."},{"key":"nanoad857ebib19","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1177\/1352458514560928","article-title":"Corpus callosum atrophy is strongly associated with cognitive impairment in multiple sclerosis: results of a 17-year longitudinal study","volume":"21","author":"Granberg","year":"2015","journal-title":"Mult. Scler."},{"key":"nanoad857ebib20","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/S0165-5728(98)00168-4","article-title":"Microglial\/macrophage accumulation during cuprizone-induced demyelination in C57BL\/6 mice","volume":"92","author":"Hiremath","year":"1998","journal-title":"J. Neuroimmunol."},{"key":"nanoad857ebib21","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/0003-2697(88)90554-4","article-title":"A spectrophotometric method for determination of catalase activity in small tissue samples","volume":"174","author":"Johansson","year":"1988","journal-title":"Anal. Biochem."},{"key":"nanoad857ebib22","doi-asserted-by":"publisher","first-page":"578","DOI":"10.4103\/1673-5374.380879","article-title":"Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis","volume":"19","author":"Junior","year":"2024","journal-title":"Neural Regen. Res."},{"key":"nanoad857ebib23","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1007\/s00401-009-0591-3","article-title":"The cuprizone animal model: new insights into an old story","volume":"118","author":"Kipp","year":"2009","journal-title":"Acta Neuropathol."},{"key":"nanoad857ebib24","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1097\/00005072-195312040-00008","article-title":"A method for the combined staining of cells and fibers in the nervous system","volume":"12","author":"Kl\u00fcver","year":"1953","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"nanoad857ebib25","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1177\/1352458518800827.Current","article-title":"Current advancements in promoting remyelination in multiple sclerosis","volume":"25","author":"Kremer","year":"2020","journal-title":"Mult. Scler. J."},{"key":"nanoad857ebib26","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1007\/s12031-019-01312-0","article-title":"Animal weight is an important variable for reliable cuprizone-induced demyelination","volume":"68","author":"Leopold","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"nanoad857ebib27","doi-asserted-by":"publisher","first-page":"703","DOI":"10.2217\/17435889.3.5.703","article-title":"Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats","volume":"3","author":"Longmire","year":"2008","journal-title":"Nanomedicine"},{"key":"nanoad857ebib28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13024-022-00538-8","article-title":"Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination","volume":"17","author":"Martin","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"nanoad857ebib29","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1750-3639.2001.tb00385.x","article-title":"The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system","volume":"11","author":"Matsushima","year":"2001","journal-title":"Brain Pathol."},{"key":"nanoad857ebib30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12951-015-0143-z","article-title":"Reduced graphene oxide induces transient blood-brain barrier opening: an in vivo study","volume":"13","author":"Mendon\u00e7a","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"nanoad857ebib31","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12951-016-0206-9","article-title":"Reduced graphene oxide: nanotoxicological profile in rats","volume":"14","author":"Mendonca","year":"2016","journal-title":"J. Neuroimmunol."},{"key":"nanoad857ebib32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2023.1254586","article-title":"Astrogliosis in multiple sclerosis and neuro-inflammation: what role for the notch pathway?","volume":"14","author":"Mora","year":"2023","journal-title":"Front. Immunol."},{"key":"nanoad857ebib33","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"nanoad857ebib34","doi-asserted-by":"publisher","first-page":"2950","DOI":"10.3390\/ijms24032950","article-title":"The protective role of glutathione on zinc-induced neuron death after brain injuries","volume":"24","author":"Park","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"nanoad857ebib35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119226","article-title":"Graphene oxide and reduced graphene oxide-based scaffolds in regenerative medicine","volume":"580","author":"Raslan","year":"2020","journal-title":"Int. J. Pharm."},{"key":"nanoad857ebib36","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"nanoad857ebib37","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1002\/glia.24148","article-title":"The roles of microglia and astrocytes in phagocytosis and myelination: insights from the cuprizone model of multiple sclerosis","volume":"70","author":"Sen","year":"2022","journal-title":"Glia"},{"key":"nanoad857ebib38","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s12291-013-0408-y","article-title":"Alkaline phosphatase: an overview","volume":"29","author":"Sharma","year":"2014","journal-title":"Indian J. Clin. Biochem."},{"key":"nanoad857ebib39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0234001","article-title":"Increased blood-brain barrier hyperpermeability coincides with mast cell activation early under cuprizone administration","volume":"15","author":"Shelestak","year":"2020","journal-title":"PLoS One"},{"key":"nanoad857ebib40","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1152\/physrev.00031.2018","article-title":"Myelin in the central nervous system: structure, function, and pathology","volume":"99","author":"Stadelmann","year":"2019","journal-title":"Physiol. Rev."},{"key":"nanoad857ebib41","first-page":"307","article-title":"Status spongiosus of CNS and hepatic changes induced by cuprizone (biscyclohexanone oxalyldihydrazone)","volume":"54","author":"Suzuki","year":"1969","journal-title":"Am. J. Pathol."},{"key":"nanoad857ebib42","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1111\/vcp.12082","article-title":"Use of optimized aminotransferase methods in regulated preclinical studies","volume":"42","author":"Tarrant","year":"2013","journal-title":"Vet. Clin. Pathol."},{"key":"nanoad857ebib43","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222313047","article-title":"An update on graphene-based nanomaterials for neural growth and central nervous system regeneration","volume":"22","author":"Tupone","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"nanoad857ebib44","doi-asserted-by":"publisher","first-page":"129","DOI":"10.2174\/1570159x15666170717120343","article-title":"Five decades of cuprizone, an updated model to replicate demyelinating diseases","volume":"17","author":"Vega-Riquer","year":"2019","journal-title":"Curr. Neuropharmacol."},{"key":"nanoad857ebib45","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.actbio.2018.11.032","article-title":"In vitro and in vivo studies of electroactive reduced graphene oxide-modified nanofiber scaffolds for peripheral nerve regeneration","volume":"84","author":"Wang","year":"2019","journal-title":"Acta Biomater."},{"key":"nanoad857ebib46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/adma.202004555","article-title":"Reduced graphene oxide-encapsulated microfiber patterns enable controllable formation of neuronal-like networks","volume":"32","author":"Wang","year":"2020","journal-title":"Adv. Mater."},{"key":"nanoad857ebib47","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/s11671-010-9751-6","article-title":"Biocompatibility of graphene oxide biocompatibility of graphene oxide","volume":"6","author":"Wang","year":"2010","journal-title":"Nanoscale Res. Lett."},{"key":"nanoad857ebib48","first-page":"337","article-title":"The estimation of red cell superoxide dismutase activity","volume":"85","author":"Winterbourn","year":"1975","journal-title":"J. Lab. Clin. Med."},{"key":"nanoad857ebib49","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1177\/1352458513496880","article-title":"The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients","volume":"20","author":"Yaldizli","year":"2014","journal-title":"Mult. Scler. J."},{"key":"nanoad857ebib50","doi-asserted-by":"publisher","first-page":"843","DOI":"10.3390\/cells9040843","article-title":"The cuprizone model: dos and do nots","volume":"9","author":"Zhan","year":"2020","journal-title":"Cells"},{"key":"nanoad857ebib51","doi-asserted-by":"publisher","DOI":"10.1016\/j.compositesa.2022.107051","article-title":"Recent advances on graphene: synthesis, properties and applications","volume":"160","author":"Zhang","year":"2022","journal-title":"Composites A"}],"container-title":["Nanotechnology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T13:44:34Z","timestamp":1729518274000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6528\/ad857e"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,21]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,10,21]]},"published-print":{"date-parts":[[2025,1,13]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6528\/ad857e","relation":{},"ISSN":["0957-4484","1361-6528"],"issn-type":[{"value":"0957-4484","type":"print"},{"value":"1361-6528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,21]]},"assertion":[{"value":"The therapeutic potential of reduced graphene oxide in attenuating cuprizone-induced demyelination in mice","name":"article_title","label":"Article Title"},{"value":"Nanotechnology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2024-08-19","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-10-10","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-10-21","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}