title: Recombinant T-cell receptor ligand RTL1000 limits inflammation and decreases infarct size after experimental ischemic stroke in middle-aged mice.
abstract: We have previously demonstrated that recombinant T-cell receptor ligand 1000 (RTL1000) reduces infarct size and improves long-term functional recovery after experimental stroke in young transgenic mice expressing human leukocyte antigen DR2 (DR2-Tg). In this study, we determined the effect of RTL1000 on infarct size in 12-month-old middle-aged DR2-Tg mice, and investigated its mechanism of action. Twelve-month-old male DR2-Tg mice underwent 60min of intraluminal reversible middle cerebral artery occlusion (MCAO). Vehicle or RTL1000 was injected 4, 24, 48 and 72h after MCAO. Cortical, striatal and total hemispheric infarcts were measured 96h after stroke. Spleen and brain tissues were collected 96h after stroke for immunological analysis. Our data showed that RTL1000 significantly reduced infarct size 96h after MCAO in middle-aged male DR2-Tg mice. RTL1000 decreased the number of activated monocytes/microglia cells (CD11b(+)CD45(hi)) and CD3(+) T cells in the ischemic hemisphere. RTL1000 also reduced the percentage of total T cells and inflammatory neutrophils in the spleen. These findings suggest that RTL1000 protects against ischemic stroke in middle-aged male mice by limiting post-ischemic inflammation.
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA; Neuroimmunology Research, Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Dotson
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Libal
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA; Neuroimmunology Research, Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Lapato
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA; Neuroimmunology Research, Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bodhankar
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA; Neuroimmunology Research, Portland Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: H
authors.initials: H
authors.lastname: Offner
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR 97239, USA; The Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR 97239, USA; Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: alkayedn@ohsu.edu.
authors.forename: N J
authors.initials: NJ
authors.lastname: Alkayed
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011897:Random Allocation; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020521:Stroke / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology
chemical_list: D059811:HLA-DRB1 Chains; D018696:Neuroprotective Agents; C542328:RTL1000 protein; D011993:Recombinant Fusion Proteins
keywords: HLA-DR2 transgenic mice; immunotherapy; ischemic stroke; recombinant T-cell receptor ligand