Mucosal tolerization to E-selectin protects against memory dysfunction and white matter damage in a vascular cognitive impairment model.
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.
Wakita
Hideaki
H
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4476, USA.
Ruetzler
Christl
C
Illoh
Kachikwu O
KO
Chen
Yong
Y
Takanohashi
Asako
A
Spatz
Maria
M
Hallenbeck
John M
JM
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
D019040:E-Selectin; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha