title: Partial MHC Constructs Treat Thromboembolic Ischemic Stroke Characterized by Early Immune Expansion.
abstract: Inflammation and thrombosis are tightly linked, with inflammation contributing to thromboembolism and to stroke outcome. Thromboembolism is a frequent cause of ischemic stroke; yet, the most used occlusion mouse models of experimental stroke do not effectively replicate thromboembolism. Our group recently described a novel thromboembolic mouse model of stroke that successfully occludes the middle cerebral artery with high reproducibility. In the current study, we characterize the peripheral and local immune outcomes as well as the ischemic response to immune therapy in a clinically relevant mouse model of thromboembolic stroke. Brain and spleen tissues were harvested 24 h after thromboembolic stroke and cells immunophenotyped by flow cytometry. We observed a significant increase in neutrophils and early activated T cells in the spleen and an increase in neutrophils and activated monocytes/microglia in the ischemic cortex after thromboembolic stroke. Moreover, as was shown previously for transient MCAO models, treatment of thromboembolic stroke with partial MHC constructs significantly reduced ischemic damage indicating an equivalent effect of this immune-based therapy in the thromboembolic model that better mimics the pathophysiology of human stroke.
authors.affiliation: Neuroimmunology Research, VA Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Abby L
authors.initials: AL
authors.lastname: Dotson
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Libal
authors.affiliation: Department of Neurology, Oregon Health & Science University, Portland, OR, USA.|Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.|Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, 97239, USA.
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Alkayed
authors.affiliation: Neuroimmunology Research, VA Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA. offnerva@ohsu.edu.|Department of Neurology, Oregon Health & Science University, Portland, OR, USA. offnerva@ohsu.edu.|Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA. offnerva@ohsu.edu.
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D004195:Disease Models, Animal; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000188:drug therapy; D008285:Major Histocompatibility Complex; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D020521:Stroke / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D013923:Thromboembolism / Q000150:complications*
chemical_list: C542328:RTL1000 protein; D011993:Recombinant Fusion Proteins
keywords: Immune response; Neuroinflammation; RTL1000; Therapy; Thromboembolic stroke