{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:15:53Z","timestamp":1790320553001,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"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":"publisher","award":["R25 GM071745"],"award-info":[{"award-number":["R25 GM071745"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 MH104134-01"],"award-info":[{"award-number":["R01 MH104134-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 MH111389-01"],"award-info":[{"award-number":["R01 MH111389-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Dimethyl fumarate (DMF), an antioxidant\/anti-inflammatory drug approved for the treatment of multiple sclerosis, induces antioxidant enzymes, in part through transcriptional upregulation. We hypothesized that DMF administration to simian immunodeficiency virus (SIV)-infected rhesus macaques would induce antioxidant enzyme expression and reduce oxidative injury and inflammation throughout the brain. Nine SIV-infected, CD8+-T-lymphocyte-depleted rhesus macaques were studied. Five received oral DMF prior to the SIV infection and through to the necropsy day. Protein expression was analyzed in 11 brain regions, as well as the thymus, liver, and spleen, using Western blot and immunohistochemistry for antioxidant, inflammatory, and neuronal proteins. Additionally, oxidative stress was determined in brain sections using immunohistochemistry (8-OHdG, 3NT) and optical redox imaging of oxidized flavoproteins containing flavin adenine dinucleotide (Fp) and reduced nicotinamide adenine dinucleotide (NADH). The DMF treatment was associated with no changes in virus replication; higher expressions of the antioxidant enzymes NQO1, GPX1, and HO-1 in the brain and PRDX1 and HO-2 in the spleen; lower levels of 8-OHdG and 3NT; a lower optical redox ratio. The DMF treatment was also associated with increased expressions of cell-adhesion molecules (VCAM-1, ICAM-1) and no changes in HLA-DR, CD68, GFAP, NFL, or synaptic proteins. The concordantly increased brain antioxidant enzyme expressions and reduced oxidative stress in DMF-treated SIV-infected macaques suggest that DMF could limit oxidative stress throughout the brain through effective induction of the endogenous antioxidant response. We propose that DMF could potentially induce neuroprotective brain responses in persons living with HIV.<\/jats:p>","DOI":"10.3390\/antiox10030416","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T12:08:01Z","timestamp":1615291681000},"page":"416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9674-1417","authenticated-orcid":false,"given":"Yoelvis","family":"Garcia-Mesa","sequence":"first","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5127-2629","authenticated-orcid":false,"given":"He N.","family":"Xu","sequence":"additional","affiliation":[{"name":"Britton Chance Laboratory of Redox Imaging, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Vance","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Analise L.","family":"Gruenewald","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Garza","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecily","family":"Midkiff","sequence":"additional","affiliation":[{"name":"Department of Pathology, TNPRC, Tulane University, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Alvarez-Hernandez","sequence":"additional","affiliation":[{"name":"Department of Pathology, TNPRC, Tulane University, Covington, LA 70433, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8224-9317","authenticated-orcid":false,"given":"Alexander J.","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7596-5726","authenticated-orcid":false,"given":"Dennis L.","family":"Kolson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1038\/nm1511","article-title":"Microbial translocation is a cause of systemic immune activation in chronic HIV infection","volume":"12","author":"Brenchley","year":"2006","journal-title":"Nat. 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