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B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice

Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery oc...

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Autores principales: Ortega, Sterling B., Torres, Vanessa O., Latchney, Sarah E., Whoolery, Cody W., Noorbhai, Ibrahim Z., Poinsatte, Katie, Selvaraj, Uma M., Benson, Monica A., Meeuwissen, Anouk J. M., Plautz, Erik J., Kong, Xiangmei, Ramirez, Denise M., Ajay, Apoorva D., Meeks, Julian P., Goldberg, Mark P., Monson, Nancy L., Eisch, Amelia J., Stowe, Ann M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060723/
https://www.ncbi.nlm.nih.gov/pubmed/32051245
http://dx.doi.org/10.1073/pnas.1913292117
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author Ortega, Sterling B.
Torres, Vanessa O.
Latchney, Sarah E.
Whoolery, Cody W.
Noorbhai, Ibrahim Z.
Poinsatte, Katie
Selvaraj, Uma M.
Benson, Monica A.
Meeuwissen, Anouk J. M.
Plautz, Erik J.
Kong, Xiangmei
Ramirez, Denise M.
Ajay, Apoorva D.
Meeks, Julian P.
Goldberg, Mark P.
Monson, Nancy L.
Eisch, Amelia J.
Stowe, Ann M.
author_facet Ortega, Sterling B.
Torres, Vanessa O.
Latchney, Sarah E.
Whoolery, Cody W.
Noorbhai, Ibrahim Z.
Poinsatte, Katie
Selvaraj, Uma M.
Benson, Monica A.
Meeuwissen, Anouk J. M.
Plautz, Erik J.
Kong, Xiangmei
Ramirez, Denise M.
Ajay, Apoorva D.
Meeks, Julian P.
Goldberg, Mark P.
Monson, Nancy L.
Eisch, Amelia J.
Stowe, Ann M.
author_sort Ortega, Sterling B.
collection PubMed
description Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20(+) (hCD20(+)) transgenic mice to continuously deplete hCD20(+)-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain.
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spelling pubmed-70607232020-03-13 B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice Ortega, Sterling B. Torres, Vanessa O. Latchney, Sarah E. Whoolery, Cody W. Noorbhai, Ibrahim Z. Poinsatte, Katie Selvaraj, Uma M. Benson, Monica A. Meeuwissen, Anouk J. M. Plautz, Erik J. Kong, Xiangmei Ramirez, Denise M. Ajay, Apoorva D. Meeks, Julian P. Goldberg, Mark P. Monson, Nancy L. Eisch, Amelia J. Stowe, Ann M. Proc Natl Acad Sci U S A Biological Sciences Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20(+) (hCD20(+)) transgenic mice to continuously deplete hCD20(+)-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain. National Academy of Sciences 2020-03-03 2020-02-12 /pmc/articles/PMC7060723/ /pubmed/32051245 http://dx.doi.org/10.1073/pnas.1913292117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Ortega, Sterling B.
Torres, Vanessa O.
Latchney, Sarah E.
Whoolery, Cody W.
Noorbhai, Ibrahim Z.
Poinsatte, Katie
Selvaraj, Uma M.
Benson, Monica A.
Meeuwissen, Anouk J. M.
Plautz, Erik J.
Kong, Xiangmei
Ramirez, Denise M.
Ajay, Apoorva D.
Meeks, Julian P.
Goldberg, Mark P.
Monson, Nancy L.
Eisch, Amelia J.
Stowe, Ann M.
B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice
title B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice
title_full B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice
title_fullStr B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice
title_full_unstemmed B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice
title_short B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice
title_sort b cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060723/
https://www.ncbi.nlm.nih.gov/pubmed/32051245
http://dx.doi.org/10.1073/pnas.1913292117
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