{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T18:10:12Z","timestamp":1787767812739,"version":"build-2784847793"},"reference-count":81,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2019,6,30]],"date-time":"2019-06-30T00:00:00Z","timestamp":1561852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Culture of Lower Saxony","award":["N-RENNT"],"award-info":[{"award-number":["N-RENNT"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) Background: Canine distemper virus (CDV)-induced demyelinating leukoencephalitis (CDV-DL) in dogs and Theiler\u2019s murine encephalomyelitis (TME) virus (TMEV)-induced demyelinating leukomyelitis (TMEV-DL) are virus-induced demyelinating conditions mimicking Multiple Sclerosis (MS). Reactive oxygen species (ROS) can induce the degradation of lipids and nucleic acids to characteristic metabolites such as oxidized lipids, malondialdehyde, and 8-hydroxyguanosine. The hypothesis of this study is that ROS are key effector molecules in the pathogenesis of myelin membrane breakdown in CDV-DL and TMEV-DL. (2) Methods: ROS metabolites and antioxidative enzymes were assessed using immunofluorescence in cerebellar lesions of naturally CDV-infected dogs and spinal cord tissue of TMEV-infected mice. The transcription of selected genes involved in ROS generation and detoxification was analyzed using gene-expression microarrays in CDV-DL and TMEV-DL. (3) Results: Immunofluorescence revealed increased amounts of oxidized lipids, malondialdehyde, and 8-hydroxyguanosine in CDV-DL while TMEV-infected mice did not reveal marked changes. In contrast, microarray-analysis showed an upregulated gene expression associated with ROS generation in both diseases. (4) Conclusion: In summary, the present study demonstrates a similar upregulation of gene-expression of ROS generation in CDV-DL and TMEV-DL. However, immunofluorescence revealed increased accumulation of ROS metabolites exclusively in CDV-DL. These results suggest differences in the pathogenesis of demyelination in these two animal models.<\/jats:p>","DOI":"10.3390\/ijms20133217","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T03:23:59Z","timestamp":1561951439000},"page":"3217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Reactive Oxygen Species Are Key Mediators of Demyelination in Canine Distemper Leukoencephalitis but not in Theiler\u2019s Murine Encephalomyelitis"],"prefix":"10.3390","volume":"20","author":[{"given":"Friederike","family":"Attig","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience, D-30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Spitzbarth","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience, D-30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno","family":"Kalkuhl","sequence":"additional","affiliation":[{"name":"Department of Non-clinical Drug Safety, Boehringer Ingelheim Pharma GmbH &amp; Co.KG, D-88397 Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Deschl","sequence":"additional","affiliation":[{"name":"Department of Non-clinical Drug Safety, Boehringer Ingelheim Pharma GmbH &amp; Co.KG, D-88397 Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Puff","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Baumg\u00e4rtner","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience, D-30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9403-1224","authenticated-orcid":false,"given":"Reiner","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany"},{"name":"Center for Systems Neuroscience, D-30559 Hannover, Germany"},{"name":"Institute for Veterinary Pathology, Faculty of Veterinary Medicine, University of Leipzig, D-04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.molmed.2013.11.007","article-title":"Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis","volume":"20","author":"Witte","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"L1005","DOI":"10.1152\/ajplung.2000.279.6.L1005","article-title":"Reactive oxygen species in cell signaling","volume":"279","author":"Thannickal","year":"2000","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physrev.00018.2001","article-title":"Free radicals in the physiological control of cell function","volume":"82","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1750-3639.1999.tb00212.x","article-title":"Demyelination: The role of reactive oxygen and nitrogen species","volume":"9","author":"Smith","year":"1999","journal-title":"Brain Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00415-004-0348-9","article-title":"The role of oxidative stress in the pathogenesis of multiple sclerosis: The need for effective antioxidant therapy","volume":"251","author":"Melamed","year":"2004","journal-title":"J. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ejmech.2015.04.040","article-title":"The role of antioxidants in the chemistry of oxidative stress: A review","volume":"97","author":"Pisoschi","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1161\/01.ATV.10.3.325","article-title":"Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein","volume":"10","author":"Palinski","year":"1990","journal-title":"Arteriosclerosis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1172\/JCI118853","article-title":"Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E-deficient mice. Demonstration of epitopes of oxidized low density lipoprotein in human plasma","volume":"98","author":"Palinski","year":"1996","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1172\/JCI4533","article-title":"Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins","volume":"103","author":"Horkko","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/ana.23974","article-title":"Iron and neurodegeneration in the multiple sclerosis brain","volume":"74","author":"Hametner","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1093\/brain\/awr128","article-title":"Oxidative damage in multiple sclerosis lesions","volume":"134","author":"Haider","year":"2011","journal-title":"Brain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cccn.2003.09.010","article-title":"Urinary 8-OHdG: A marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics","volume":"339","author":"Wu","year":"2004","journal-title":"Clin. Chim Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/oxfordjournals.bmb.a069695","article-title":"Lipids and the structure of myelin","volume":"14","author":"Finean","year":"1958","journal-title":"Br. Med. Bull"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.tcb.2011.06.004","article-title":"Central nervous system myelin: Structure, synthesis and assembly","volume":"21","author":"Aggarwal","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1194\/jlr.R009761","article-title":"Lipid metabolism in myelinating glial cells: Lessons from human inherited disorders and mouse models","volume":"52","author":"Chrast","year":"2011","journal-title":"J. Lipid Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.freeradbiomed.2013.05.027","article-title":"SOD2 in mitochondrial dysfunction and neurodegeneration","volume":"62","author":"Flynn","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0003-9861(52)90194-X","article-title":"The mechanism of catalase action. I. Steady-state analysis","volume":"37","author":"Chance","year":"1952","journal-title":"Arch. Biochem. Biophys"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/BF00687712","article-title":"Naturally occurring canine distemper virus encephalitis: Distribution and expression of viral polypeptides in nervous tissues","volume":"78","author":"Reinacher","year":"1989","journal-title":"Acta Neuropathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1177\/43.12.8537642","article-title":"Immunocytochemical localization of catalase in the central nervous system of the rat","volume":"43","author":"Moreno","year":"1995","journal-title":"J. Histochem Cytochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0368-1742(26)80021-9","article-title":"Studies in dog-distemper: II.\u2014Experimental distemper in the dog","volume":"39","author":"Dunkin","year":"1926","journal-title":"J. Comp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1748-5827.1992.tb01024.x","article-title":"Neurological manifestations of canine distemper virus infection","volume":"33","author":"Tipold","year":"1992","journal-title":"J. Small Anim Pr."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Carvalho, O.V., Botelho, C.V., Ferreira, C.G.T., Scherer, P.O., Soares-Martins, J.A.P., Almeida, M.R., and Silva J\u00fanior, A. (2012). Immunopathogenic and neurological mechanisms of canine distemper virus. Adv. Virus Res., 2012.","DOI":"10.1155\/2012\/163860"},{"key":"ref_23","unstructured":"Mendez-Vilas, A. (2010). Canine distemper virus and multiple sclerosis: A real or an anecdotal association. Current Research, Technology and Education Topics in Applied Microbiology and Microbial. Biotechnology. Sao Paulo: Formatex, Formatex Research Center. [2nd ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vetimm.2008.09.023","article-title":"Pathogenesis and immunopathology of systemic and nervous canine distemper","volume":"127","author":"Beineke","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s00401-010-0644-7","article-title":"Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein","volume":"119","author":"Zurbriggen","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s004010050518","article-title":"Up-regulation of major histocompatibility complex class II antigen expression in the central nervous system of dogs with spontaneous canine distemper virus encephalitis","volume":"92","author":"Alldinger","year":"1996","journal-title":"Acta Neuropathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00684797","article-title":"Early events in canine distemper demyelinating encephalomyelitis","volume":"46","author":"Summers","year":"1979","journal-title":"Acta Neuropathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.3390\/v6072571","article-title":"New aspects of the pathogenesis of canine distemper leukoencephalitis","volume":"6","author":"Lempp","year":"2014","journal-title":"Viruses"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s00401-004-0958-4","article-title":"Demyelination in canine distemper virus infection: A review","volume":"109","author":"Vandevelde","year":"2005","journal-title":"Acta Neuropathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s004010050767","article-title":"Oligodendroglial pathology in canine distemper","volume":"95","author":"Zurbriggen","year":"1997","journal-title":"Acta Neuropathol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ulrich, R., Puff, C., Wewetzer, K., Kalkuhl, A., Deschl, U., and Baumgartner, W. (2014). Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095917"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1128\/jvi.60.3.1163-1165.1986","article-title":"Theiler\u2019s virus genome is closely related to that of encephalomyocarditis virus, the prototype cardiovirus","volume":"60","author":"Ozden","year":"1986","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1128\/jvi.61.5.1507-1516.1987","article-title":"Analysis of the complete nucleotide sequence of the picornavirus Theiler\u2019s murine encephalomyelitis virus indicates that it is closely related to cardioviruses","volume":"61","author":"Pevear","year":"1987","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1128\/CMR.17.1.174-207.2004","article-title":"Theiler\u2019s virus infection: A model for multiple sclerosis","volume":"17","author":"Oleszak","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1084\/jem.65.5.705","article-title":"Spontaneous Encephalomyelitis of Mice, A New Virus Disease","volume":"65","author":"Theiler","year":"1937","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.pneurobio.2012.11.003","article-title":"Viral models of multiple sclerosis: Neurodegeneration and demyelination in mice infected with Theiler\u2019s virus","volume":"101","author":"Mecha","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/j.1582-4934.2008.00646.x","article-title":"Machine learning approach identifies new pathways associated with demyelination in a viral model of multiple sclerosis","volume":"14","author":"Ulrich","year":"2010","journal-title":"J. Cell Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0378-1135(95)00021-2","article-title":"The neurobiology of canine distemper virus infection","volume":"44","author":"Vandevelde","year":"1995","journal-title":"Vet. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1365-2990.2008.00956.x","article-title":"Limited remyelination in Theiler\u2019s murine encephalomyelitis due to insufficient oligodendroglial differentiation of nerve\/glial antigen 2 (NG2)-positive putative oligodendroglial progenitor cells","volume":"34","author":"Ulrich","year":"2008","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/brain\/aws012","article-title":"NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury","volume":"135","author":"Fischer","year":"2012","journal-title":"Brain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.bbadis.2011.10.017","article-title":"Antioxidant therapies in traumatic brain and spinal cord injury","volume":"1822","author":"Bains","year":"2012","journal-title":"Biochim. Biophys Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pathophys.2010.04.004","article-title":"The relevance of animal models in multiple sclerosis research","volume":"18","author":"Denic","year":"2011","journal-title":"Pathophysiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.ejphar.2015.03.042","article-title":"Animal models of multiple sclerosis","volume":"759","author":"Procaccini","year":"2015","journal-title":"Eur. J. Pharm."},{"key":"ref_44","first-page":"361","article-title":"Animal model of human disease: Subacute sclerosing panencephalitis, multiple sclerosis; animal model: Distemper-associated demyelinating encephalomyelitis","volume":"78","author":"Koestner","year":"1975","journal-title":"Am. J. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00401-014-1263-5","article-title":"Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models","volume":"128","author":"Schuh","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/ana.410110202","article-title":"Experimental models of virus-induced demyelination of the central nervous system","volume":"11","author":"Rabinowitz","year":"1982","journal-title":"Ann. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive oxygen species in inflammation and tissue injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid Redox Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/0891-5849(96)00131-1","article-title":"Oxidative stress during viral infection: A review","volume":"21","author":"Schwarz","year":"1996","journal-title":"Free Radic Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1006\/viro.2000.0646","article-title":"Differential expression of TGF-\u03b2, IL-2, and other cytokines in the CNS of Theiler\u2019s murine encephalomyelitis virus-infected susceptible and resistant strains of mice","volume":"278","author":"Chang","year":"2000","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bbadis.2009.07.002","article-title":"Is multiple sclerosis a mitochondrial disease?","volume":"1802","author":"Mao","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.tcb.2005.01.002","article-title":"Regulation of innate immunity by Rho GTPases","volume":"15","author":"Bokoch","year":"2005","journal-title":"Trends Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1007\/s00125-013-2849-5","article-title":"Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin","volume":"56","author":"Asahara","year":"2013","journal-title":"Diabetologia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1242\/jcs.114.15.2713","article-title":"Rho GTPases and cell migration","volume":"114","author":"Ridley","year":"2001","journal-title":"J. Cell Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/bies.20558","article-title":"GTP-binding proteins of the Rho\/Rac family: Regulation, effectors and functions in vivo","volume":"29","author":"Bustelo","year":"2007","journal-title":"Bioessays"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1007\/s11064-007-9290-4","article-title":"Brain iron toxicity: Differential responses of astrocytes, neurons, and endothelial cells","volume":"32","author":"Gaasch","year":"2007","journal-title":"Neurochem. Res."},{"key":"ref_57","first-page":"S64","article-title":"Iron and brain disorders","volume":"121","author":"Sadrzadeh","year":"2004","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_58","first-page":"647","article-title":"Progressive multiple sclerosis: Pathology and pathogenesis","volume":"8","author":"Lassmann","year":"2012","journal-title":"Nat. Rev. Neurosci"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1093\/brain\/awp046","article-title":"Mitochondrial changes within axons in multiple sclerosis","volume":"132","author":"Mahad","year":"2009","journal-title":"Brain"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1093\/brain\/awn105","article-title":"Mitochondrial defects in acute multiple sclerosis lesions","volume":"131","author":"Mahad","year":"2008","journal-title":"Brain"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1006\/scdb.2001.0282","article-title":"Reactive oxygen species and mitochondrial diseases","volume":"12","author":"Kirkinezos","year":"2001","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1177\/002215540305100606","article-title":"Expression of catalase mRNA and protein in adult rat brain: Detection by nonradioactive in situ hybridization with signal amplification by catalyzed reporter deposition (ISH\u2013CARD) and immunohistochemistry (IHC)\/immunofluorescence (IF)","volume":"51","author":"Schad","year":"2003","journal-title":"J. Histochem. Cytochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"467","DOI":"10.3109\/02713688909000027","article-title":"Antioxidant enzyme suppression of demyelination in experimental optic neuritis","volume":"8","author":"Guy","year":"1989","journal-title":"Curr. Eye Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.freeradbiomed.2008.09.023","article-title":"Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression","volume":"45","author":"Schreibelt","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00401-007-0307-5","article-title":"Vimentin-positive astrocytes in canine distemper: A target for canine distemper virus especially in chronic demyelinating lesions?","volume":"114","author":"Seehusen","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1111\/nan.12133","article-title":"STAT3 represents a molecular switch possibly inducing astroglial instead of oligodendroglial differentiation of oligodendroglial progenitor cells in Theiler\u2019s murine encephalomyelitis","volume":"41","author":"Sun","year":"2015","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.cvsm.2010.05.007","article-title":"The pathogenesis and treatment of acute spinal cord injuries in dogs","volume":"40","author":"Olby","year":"2010","journal-title":"Vet. Clin. North. Am. Food Anim Pr."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Freundt-Revilla, J., Kegler, K., Baumg\u00e4rtner, W., and Tipold, A. (2017). Spatial distribution of cannabinoid receptor type 1 (CB1) in normal canine central and peripheral nervous system. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181064"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Uhde, A.-K., Herder, V., Khan, M.A., Ciurkiewicz, M., Schaudien, D., Teich, R., Floess, S., Baumg\u00e4rtner, W., Huehn, J., and Beineke, A. (2016). Viral Infection of the Central Nervous System Exacerbates Interleukin-10 Receptor Deficiency-Mediated Colitis in SJL Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161883"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/bioinformatics\/19.2.185","article-title":"A comparison of normalization methods for high density oligonucleotide array data based on variance and bias","volume":"19","author":"Bolstad","year":"2003","journal-title":"Bioinformatics"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1177\/0300985817709887","article-title":"Microarray-based gene expression analysis for veterinary pathologists: A review","volume":"54","author":"Raddatz","year":"2017","journal-title":"Vet. Pathol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.smim.2013.01.002","article-title":"New tricks from an old dog: Mitochondrial redox signaling in cellular inflammation","volume":"24","author":"Pelletier","year":"2012","journal-title":"Semin Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s12640-012-9345-4","article-title":"Effect of l-Tyrosine In Vitro and In Vivo on Energy Metabolism Parameters in Brain and Liver of Young Rats","volume":"23","author":"Ferreira","year":"2013","journal-title":"Neurotox. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1089\/ars.2005.7.1140","article-title":"Production of reactive oxygen species in brain mitochondria: Contribution by electron transport chain and non\u2013electron transport chain sources","volume":"7","year":"2005","journal-title":"Antioxid Redox Signal."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/ana.410390508","article-title":"Brain protein and alpha-ketoglutarate dehydrogenase complex activity in Alzheimer\u2019s disease","volume":"39","author":"Mastrogiacoma","year":"1996","journal-title":"Ann. Neurol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/j.str.2008.10.010","article-title":"Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: Role of disordered phosphorylation loops","volume":"16","author":"Kato","year":"2008","journal-title":"Structure"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"12819","DOI":"10.1073\/pnas.95.22.12819","article-title":"The mechanism of proton pumping by cytochrome c oxidasex127e [comments]","volume":"95","author":"Michel","year":"1998","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1146\/annurev.biophys.27.1.329","article-title":"Cytochrome c oxidase: Structure and spectroscopy","volume":"27","author":"Michel","year":"1998","journal-title":"Annu. Rev. Biophys Biomol. Struct."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1021\/bi9925322","article-title":"Proton translocation by cytochrome c oxidase: A rejoinder to recent criticism","volume":"39","author":"Wikstrom","year":"2000","journal-title":"Biochemistry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.bbadis.2010.06.011","article-title":"Radical changes in multiple sclerosis pathogenesis","volume":"1812","author":"Witte","year":"2011","journal-title":"Biochim. Biophys Acta Mol. Basis Dis."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/13\/3217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:02:37Z","timestamp":1760187757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/13\/3217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,30]]},"references-count":81,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["ijms20133217"],"URL":"https:\/\/doi.org\/10.3390\/ijms20133217","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,30]]}}}