title: T cell immunity to glatiramer acetate ameliorates cognitive deficits induced by chronic cerebral hypoperfusion by modulating the microenvironment.
abstract: Vascular 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.
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Changjuan
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ma
authors.affiliation: Center for Basic Medical Science Research, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Tianjin Huanhu Hospital, Tianjin 300060, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000150:complications* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015140:Dementia, Vascular / Q000209:etiology; D004195:Disease Models, Animal; D000068717:Glatiramer Acetate / Q000276:immunology* / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: C100745:Aif1 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D000068717:Glatiramer Acetate