T cell immunity to glatiramer acetate ameliorates cognitive deficits induced by chronic cerebral hypoperfusion by modulating the microenvironment

• DOI: 10.1038/srep14308
• Publication Date: 2015-09-22T09:54:54Z
• Authors: Li Chen; Yang Yao; Changjuan Wei; Yanan Sun; Xiaofeng Ma; Rongxin Zhang; Xiaolin Xu; Junwei Hao
• Keywords: Male; 0301 basic medicine; Behavior, Animal; Brain-Derived Neurotrophic Factor; Dementia, Vascular; T-Lymphocytes; Calcium-Binding Proteins; Long-Term Potentiation; Microfilament Proteins; Glatiramer Acetate; Hippocampus; Article; Brain Ischemia; Rats; 3. Good health; Disease Models, Animal; 03 medical and health sciences; Glial Fibrillary Acidic Protein; Animals; Cytokines; Cognition Disorders; Maze Learning

AbstractVascular dementia (VaD) is a progressive and highly prevalent disorder. However, in a very large majority of cases, a milieu of cellular and molecular events common for multiple neurodegenerative diseases is involved. Our work focused on whether the immunomodulating effect of glatiramer acetate (GA) could restore normalcy to the microenvironment and ameliorate cognitive decline induced by chronic cerebral hypoperfusion. We assessed cognitive function by rats’ performance in a Morris water maze (MWM), electrophysiological recordings and by pathologic changes. The results suggest that GA reduced cognitive deficits by reestablishing an optimal microenvironment such as increasing expression of the brain-derived neurotrophic factor (BDNF) and modulating the Th1/Th2 cytokine balance in the hippocampus. When microenvironmental homeostasis is restored, cholinergic activity becomes involved in ameliorating cellular damage. Since vaccination with GA can boost “protective autoimmunity” in this way, a similar strategy may have therapeutic potential for alleviating VaD disease.