title: Mucosal tolerization to E-selectin protects against memory dysfunction and white matter damage in a vascular cognitive impairment model.
abstract: Vascular cognitive impairment (VCI) is the second most prevalent type of dementia in the world. The white matter damage that characterizes the common subcortical ischemic form of VCI can be modeled by ligating both common carotid arteries in the Wistar rat to induce protracted cerebral hypoperfusion. In this model, we find that repetitive intranasal administration of recombinant E-selectin to induce mucosal tolerance and to target immunomodulation to activating blood vessels potently suppresses both white matter (and possibly gray matter) damage and markers of vessel activation (tumor necrosis factor and E-selectin); it also preserves behavioral function in T-maze spontaneous alternation, T-maze spatial discrimination memory retention, and object recognition tests. Immunomodulation may be an effective novel strategy to prevent progression of VCI.
authors.affiliation: Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4476, USA.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Wakita
authors.forename: Christl
authors.initials: C
authors.lastname: Ruetzler
authors.forename: Kachikwu O
authors.initials: KO
authors.lastname: Illoh
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Asako
authors.initials: A
authors.lastname: Takanohashi
authors.forename: Maria
authors.initials: M
authors.lastname: Spatz
authors.forename: John M
authors.initials: JM
authors.lastname: Hallenbeck
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D015140:Dementia, Vascular / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004192:Discrimination, Psychological / Q000187:drug effects; D019040:E-Selectin / Q000494:pharmacology*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000503:physiopathology; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D018928:Immunity, Mucosal / Q000187:drug effects / Q000502:physiology*; D007118:Immunoassay; D007155:Immunologic Factors / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019040:E-Selectin; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha