B-lymphocyte-mediated delayed cognitive impairment following stroke

Kristian P. Doyle, Lisa N. Quach, Montse Solé, Robert C. Axtell, Thuy Vi V. Nguyen, Gilberto J. Soler-Llavina, Sandra Jurado, Jullet Han, Lawrence Steinman, Frank M. Longo, Julie A. Schneider, Robert C. Malenka, Marion S. Buckwalter

Research output: Contribution to journalArticle

111 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2133-2145
Number of pages13
JournalJournal of Neuroscience
Volume35
Issue number5
DOIs
StatePublished - 2015

Keywords

  • B-lymphocyte
  • Dementia
  • Immunology
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Doyle, K. P., Quach, L. N., Solé, M., Axtell, R. C., Nguyen, T. V. V., Soler-Llavina, G. J., Jurado, S., Han, J., Steinman, L., Longo, F. M., Schneider, J. A., Malenka, R. C., & Buckwalter, M. S. (2015). B-lymphocyte-mediated delayed cognitive impairment following stroke. Journal of Neuroscience, 35(5), 2133-2145. https://doi.org/10.1523/JNEUROSCI.4098-14.2015