{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:24:50Z","timestamp":1791822290817,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Interdisziplin\u00e4res Zentrum f\u00fcr Forschung (IZKF) W\u00fcrzburg","award":["T-516"],"award-info":[{"award-number":["T-516"]}]},{"name":"University of W\u00fcrzburg","award":["T-516"],"award-info":[{"award-number":["T-516"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic stroke is associated with exacerbated tissue damage caused by the activation of immune cells and the initiation of other inflammatory processes. Dimethyl fumarate (DMF) is known to modulate the immune response, activate antioxidative pathways, and improve the blood\u2013brain barrier (BBB) after stroke. However, the specific impact of DMF on immune cells after cerebral ischemia remains unclear. In our study, male mice underwent transient middle cerebral artery occlusion (tMCAO) for 30 min and received oral DMF (15 mg\/kg) or a vehicle immediately after tMCAO, followed by twice-daily administrations for 7 days. Infarct volume was assessed on T2-weighted magnetic resonance images on days 1 and 7 after tMCAO. Brain-infiltrating immune cells (lymphocytes, monocytes) and microglia were quantified using fluorescence-activated cell sorting. DMF treatment significantly reduced infarct volumes and brain edema. On day 1 after tMCAO, DMF-treated mice showed reduced lymphocyte infiltration compared to controls, which was not observed on day 7. Monocyte and microglial cell counts did not differ between groups on either day. In the acute phase of stroke, DMF administration attenuated lymphocyte infiltration, probably due to its stabilizing effect on the BBB. This highlights the potential of DMF as a therapeutic candidate for mitigating immune cell-driven damage in stroke.<\/jats:p>","DOI":"10.3390\/ijms242115540","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T11:34:47Z","timestamp":1698147287000},"page":"15540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dimethyl Fumarate Attenuates Lymphocyte Infiltration and Reduces Infarct Size in Experimental Stroke"],"prefix":"10.3390","volume":"24","author":[{"given":"Michael K.","family":"Schuhmann","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospital W\u00fcrzburg, Josef-Schneider Strasse 11, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Langhauser","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4350-3655","authenticated-orcid":false,"given":"Lena","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital W\u00fcrzburg, Josef-Schneider Strasse 11, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6462-9495","authenticated-orcid":false,"given":"Maximilian","family":"Bellut","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital W\u00fcrzburg, Josef-Schneider Strasse 11, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1650-8875","authenticated-orcid":false,"given":"Christoph","family":"Kleinschnitz","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Fluri","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital W\u00fcrzburg, Josef-Schneider Strasse 11, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1161\/STROKEAHA.122.038733","article-title":"Thromboinflammation in Brain Ischemia: Recent Updates and Future Perspectives","volume":"53","author":"Langhauser","year":"2022","journal-title":"Stroke"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s00281-023-00994-4","article-title":"Thromboinflammatory Challenges in Stroke Pathophysiology","volume":"45","author":"Szepanowski","year":"2023","journal-title":"Semin. Immunopathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1212\/WNL.0b013e3182a4a577","article-title":"Microglia: Multiple Roles in Surveillance, Circuit Shaping, and Response to Injury","volume":"81","author":"Benarroch","year":"2013","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guruswamy, R., and ElAli, A. (2017). Complex Roles of Microglial Cells in Ischemic Stroke Pathobiology: New Insights and Future Directions. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030496"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1189\/jlb.1109766","article-title":"Inflammatory Mechanisms in Ischemic Stroke: Role of Inflammatory Cells","volume":"87","author":"Jin","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Guo, K., Luo, J., Feng, D., Wu, L., Wang, X., Xia, L., Tao, K., Wu, X., Cui, W., and He, Y. (2021). Single-Cell RNA Sequencing With Combined Use of Bulk RNA Sequencing to Reveal Cell Heterogeneity and Molecular Changes at Acute Stage of Ischemic Stroke in Mouse Cortex Penumbra Area. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.624711"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1093\/brain\/awq386","article-title":"Fumaric Acid Esters Exert Neuroprotective Effects in Neuroinflammation via Activation of the Nrf2 Antioxidant Pathway","volume":"134","author":"Linker","year":"2011","journal-title":"Brain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1742-2094-7-30","article-title":"Dimethylfumarate Inhibits Microglial and Astrocytic Inflammation by Suppressing the Synthesis of Nitric Oxide, IL-1\u03b2, TNF-\u03b1 and IL-6 in an In-Vitro Model of Brain Inflammation","volume":"7","author":"Wilms","year":"2010","journal-title":"J. Neuroinflamm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1056\/NEJMoa1206328","article-title":"Placebo-Controlled Phase 3 Study of Oral BG-12 or Glatiramer in Multiple Sclerosis","volume":"367","author":"Fox","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1056\/NEJMoa1114287","article-title":"Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis","volume":"367","author":"Gold","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/j.1365-2133.1994.tb08589.x","article-title":"Fumaric Acid Derivatives Evoke a Transient Increase in Intracellular Free Calcium Concentration and Inhibit the Proliferation of Human Keratinocytes","volume":"131","author":"Thio","year":"1994","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2174\/157015909787602788","article-title":"Fumaric Acid and Its Esters: An Emerging Treatment for Multiple Sclerosis","volume":"7","author":"Linker","year":"2009","journal-title":"Curr. Neuropharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1046\/j.1365-2133.1998.02400.x","article-title":"The Antipsoriatic Agent Dimethylfumarate Immunomodulates T-Cell Cytokine Secretion and Inhibits Cytokines of the Psoriatic Cytokine Network","volume":"139","author":"Ockenfels","year":"1998","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1002\/jnr.25202","article-title":"Mechanism of Action and Therapeutic Potential of Dimethyl Fumarate in Ischemic Stroke","volume":"101","author":"Owjfard","year":"2023","journal-title":"J. Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1172\/JCI135530","article-title":"Immune Responses to Stroke: Mechanisms, Modulation, and Therapeutic Potential","volume":"130","author":"Iadecola","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1177\/0271678X221105764","article-title":"An Intravascular Perspective on Hyper-Acute Neutrophil, T-Cell and Platelet Responses: Similarities between Human and Experimental Stroke","volume":"42","author":"Stoll","year":"2022","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s12975-016-0496-0","article-title":"Dimethyl Fumarate and Monomethyl Fumarate Promote Post-Ischemic Recovery in Mice","volume":"7","author":"Yao","year":"2016","journal-title":"Transl. Stroke Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s12035-019-01760-0","article-title":"Reactive Gliosis Contributes to Nrf2-Dependent Neuroprotection by Pretreatment with Dimethyl Fumarate or Korean Red Ginseng Against Hypoxic-Ischemia: Focus on Hippocampal Injury","volume":"57","author":"Liu","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.expneurol.2015.02.022","article-title":"Dimethyl Fumarate Attenuates Cerebral Edema Formation by Protecting the Blood\u2013Brain Barrier Integrity","volume":"266","author":"Kunze","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_21","first-page":"108","article-title":"Neuroprotective Effect of Dimethyl Fumarate in Stroke: The Role of Nuclear Factor Erythroid 2-Related Factor 2","volume":"18","author":"Safari","year":"2019","journal-title":"Iran. J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"456","DOI":"10.2174\/1567202618666211109105024","article-title":"Protective Effect of GSK-3\u03b2\/Nrf2 Mediated by Dimethyl Fumarate in Middle Cerebral Artery Embolization Reperfusion Rat Model","volume":"18","author":"Li","year":"2021","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.neuron.2008.01.003","article-title":"The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders","volume":"57","author":"Zlokovic","year":"2008","journal-title":"Neuron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.freeradbiomed.2018.11.017","article-title":"Pretreatment with Korean Red Ginseng or Dimethyl Fumarate Attenuates Reactive Gliosis and Confers Sustained Neuroprotection against Cerebral Hypoxic-Ischemic Damage by an Nrf2-Dependent Mechanism","volume":"131","author":"Liu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1212\/CPJ.0000000000000238","article-title":"Characterizing Absolute Lymphocyte Count Profiles in Dimethyl Fumarate\u2013Treated Patients with MS: Patient Management Considerations","volume":"6","author":"Fox","year":"2016","journal-title":"Neurol. Clin. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mvr.2015.12.003","article-title":"Protective Effects of Monomethyl Fumarate at the Inflamed Blood\u2013Brain Barrier","volume":"105","author":"Lim","year":"2016","journal-title":"Microvasc. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1177\/1352458517735189","article-title":"Dual Action by Fumaric Acid Esters Synergistically Reduces Adhesion to Human Endothelium","volume":"24","author":"Breuer","year":"2018","journal-title":"Mult. Scler. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/sj.jid.5700996","article-title":"Dimethylfumarate Reduces Leukocyte Rolling in Vivo through Modulation of Adhesion Molecule Expression","volume":"128","author":"Rubant","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e401","DOI":"10.1212\/NXI.0000000000000401","article-title":"Impaired T-Cell Migration to the CNS under Fingolimod and Dimethyl Fumarate","volume":"4","author":"Mathias","year":"2017","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/j.1600-0625.2011.01376.x","article-title":"Downregulation of Endothelial Adhesion Molecules by Dimethylfumarate, but Not Monomethylfumarate, and Impairment of Dynamic Lymphocyte-Endothelial Cell Interactions","volume":"20","author":"Wallbrecht","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1006\/bbrc.1997.6570","article-title":"Dimethylfumarate Is an Inhibitor of Cytokine-Induced E-Selectin, VCAM-1, and ICAM-1 Expression in Human Endothelial Cells","volume":"234","author":"Vandermeeren","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1172\/JCI72151","article-title":"Hydroxycarboxylic Acid Receptor 2 Mediates Dimethyl Fumarate\u2019s Protective Effect in EAE","volume":"124","author":"Chen","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1038\/sj.jcbfm.9600298","article-title":"Bench to Bedside: The Quest for Quality in Experimental Stroke Research","volume":"26","author":"Dirnagl","year":"2006","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1161\/CIRCRESAHA.120.316655","article-title":"CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-Inflammation in Acute Stroke","volume":"127","author":"Schuhmann","year":"2020","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1161\/01.STR.0000113692.38574.57","article-title":"Noninvasive Quantification of Brain Edema and the Space-Occupying Effect in Rat Stroke Models Using Magnetic Resonance Imaging","volume":"35","author":"Gerriets","year":"2004","journal-title":"Stroke"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1161\/STROKEAHA.113.002880","article-title":"FTY720 Ameliorates Acute Ischemic Stroke in Mice by Reducing Thrombo-Inflammation but Not by Direct Neuroprotection","volume":"44","author":"Kraft","year":"2013","journal-title":"Stroke"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:11:11Z","timestamp":1760130671000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,24]]},"references-count":36,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242115540"],"URL":"https:\/\/doi.org\/10.3390\/ijms242115540","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,24]]}}}