title: B-lymphocyte-mediated delayed cognitive impairment following stroke.
abstract: Each year, 10 million people worldwide survive the neurologic injury associated with a stroke. Importantly, stroke survivors have more than twice the risk of subsequently developing dementia compared with people who have never had a stroke. The link between stroke and the later development of dementia is not understood. There are reports of oligoclonal bands in the CSF of stroke patients, suggesting that in some people a B-lymphocyte response to stroke may occur in the CNS. Therefore, we tested the hypothesis that a B-lymphocyte response to stroke could contribute to the onset of dementia. We discovered that, in mouse models, activated B-lymphocytes infiltrate infarcted tissue in the weeks after stroke. B-lymphocytes undergo isotype switching, and IgM, IgG, and IgA antibodies are found in the neuropil adjacent to the lesion. Concurrently, mice develop delayed deficits in LTP and cognition. Genetic deficiency, and the pharmacologic ablation of B-lymphocytes using an anti-CD20 antibody, prevents the appearance of delayed cognitive deficits. Furthermore, immunostaining of human postmortem tissue revealed that a B-lymphocyte response to stroke also occurs in the brain of some people with stroke and dementia. These data suggest that some stroke patients may develop a B-lymphocyte response to stroke that contributes to dementia, and is potentially treatable with FDA-approved drugs that target B cells.
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, Department of Immunobiology, Department of Neurology, and the Arizona Center on Aging, University of Arizona, Tucson, Arizona 85724.
authors: Kristian P
authors: KP
authors: Doyle
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305.
authors: Lisa N
authors: LN
authors: Quach
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, Neurosciences Institute and Department of Biochemistry and Molecular Biology, Medicine Faculty, Universitat Autonoma de Barcelona, Barcelona 08193, Spain.
authors: Montse
authors: http://orcid.org/0000-0003-4240-6562
authors: M
authors: Solé
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305.
authors: Robert C
authors: RC
authors: Axtell
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, Department of Immunobiology, Department of Neurology, and the Arizona Center on Aging, University of Arizona, Tucson, Arizona 85724.
authors: Thuy-Vi V
authors: TV
authors: Nguyen
authors: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305.
authors: Gilberto J
authors: http://orcid.org/0000-0002-1838-401X
authors: GJ
authors: Soler-Llavina
authors: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305.
authors: Sandra
authors: S
authors: Jurado
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305.
authors: Jullet
authors: J
authors: Han
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305.
authors: Lawrence
authors: http://orcid.org/0000-0002-2437-2250
authors: L
authors: Steinman
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305.
authors: Frank M
authors: FM
authors: Longo
authors: Department of Pathology and Neurological Sciences, Rush Alzheimer's Disease Center Rush University Medical Center, Chicago, Illinois 60612, and.
authors: Julie A
authors: JA
authors: Schneider
authors: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305.
authors: Robert C
authors: RC
authors: Malenka
authors: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, Department of Neurosurgery, Stanford University School of Medicine, Stanford, California 94305 marion.buckwalter@stanford.edu.
authors: Marion S
authors: http://orcid.org/0000-0003-2807-2447
authors: MS
authors: Buckwalter
mesh_terms: D000368:Aged; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D016022:Case-Control Studies; D003704:Dementia / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D007136:Immunoglobulins
keywords: B-lymphocyte; dementia; immunology; stroke
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