B cells do not have a major pathophysiologic role in acute ischemic stroke in mice

Abstract Background Lymphocytes have been shown to play an important role in the pathophysiology of acute ischemic stroke, but the properties of B cells remain controversial. The aim of this study was to unravel the role of B cells during acute cerebral ischemia using pharmacologic B cell depletion,...

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Main Authors: Michael K. Schuhmann, Friederike Langhauser, Peter Kraft, Christoph Kleinschnitz
Format: Article
Language:English
Published: BMC 2017-06-01
Series:Journal of Neuroinflammation
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12974-017-0890-x
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spelling doaj-d5187c57171c4e37865f609ab1043ad42020-11-25T00:55:58ZengBMCJournal of Neuroinflammation1742-20942017-06-011411610.1186/s12974-017-0890-xB cells do not have a major pathophysiologic role in acute ischemic stroke in miceMichael K. Schuhmann0Friederike Langhauser1Peter Kraft2Christoph Kleinschnitz3Department of Neurology, University Hospital WürzburgDepartment of Neurology, University Hospital WürzburgDepartment of Neurology, University Hospital WürzburgDepartment of Neurology, University Hospital WürzburgAbstract Background Lymphocytes have been shown to play an important role in the pathophysiology of acute ischemic stroke, but the properties of B cells remain controversial. The aim of this study was to unravel the role of B cells during acute cerebral ischemia using pharmacologic B cell depletion, B cell transgenic mice, and adoptive B cell transfer experiments. Methods Transient middle cerebral artery occlusion (60 min) was induced in wild-type mice treated with an anti-CD20 antibody 24 h before stroke onset, JHD −/− mice and Rag1 −/− mice 24 h after adoptive B cell transfer. Stroke outcome was assessed at days 1 and 3. Infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections, and neurological scores were evaluated. The local inflammatory response was determined by real-time PCR and immunohistochemistry. Apoptosis was analyzed by TUNEL staining, and astrocyte activation was revealed using immunohistochemistry and Western blot. Results Pharmacologic depletion of B cells did not influence infarct volumes and functional outcome at day 1 after stroke. Additionally, lack of circulating B cells in JHD −/− mice also failed to influence stroke outcome at days 1 and 3. Furthermore, reconstitution of Rag1 −/− mice with B cells had no influence on infarct volumes. Conclusion Targeting B cells in experimental stroke did not influence lesion volume and functional outcome during the acute phase. Our findings argue against a major pathophysiologic role of B cells during acute ischemic stroke.http://link.springer.com/article/10.1186/s12974-017-0890-xIschemic strokeTransient middle cerebral artery occlusionB cells
collection DOAJ
language English
format Article
sources DOAJ
author Michael K. Schuhmann
Friederike Langhauser
Peter Kraft
Christoph Kleinschnitz
spellingShingle Michael K. Schuhmann
Friederike Langhauser
Peter Kraft
Christoph Kleinschnitz
B cells do not have a major pathophysiologic role in acute ischemic stroke in mice
Journal of Neuroinflammation
Ischemic stroke
Transient middle cerebral artery occlusion
B cells
author_facet Michael K. Schuhmann
Friederike Langhauser
Peter Kraft
Christoph Kleinschnitz
author_sort Michael K. Schuhmann
title B cells do not have a major pathophysiologic role in acute ischemic stroke in mice
title_short B cells do not have a major pathophysiologic role in acute ischemic stroke in mice
title_full B cells do not have a major pathophysiologic role in acute ischemic stroke in mice
title_fullStr B cells do not have a major pathophysiologic role in acute ischemic stroke in mice
title_full_unstemmed B cells do not have a major pathophysiologic role in acute ischemic stroke in mice
title_sort b cells do not have a major pathophysiologic role in acute ischemic stroke in mice
publisher BMC
series Journal of Neuroinflammation
issn 1742-2094
publishDate 2017-06-01
description Abstract Background Lymphocytes have been shown to play an important role in the pathophysiology of acute ischemic stroke, but the properties of B cells remain controversial. The aim of this study was to unravel the role of B cells during acute cerebral ischemia using pharmacologic B cell depletion, B cell transgenic mice, and adoptive B cell transfer experiments. Methods Transient middle cerebral artery occlusion (60 min) was induced in wild-type mice treated with an anti-CD20 antibody 24 h before stroke onset, JHD −/− mice and Rag1 −/− mice 24 h after adoptive B cell transfer. Stroke outcome was assessed at days 1 and 3. Infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections, and neurological scores were evaluated. The local inflammatory response was determined by real-time PCR and immunohistochemistry. Apoptosis was analyzed by TUNEL staining, and astrocyte activation was revealed using immunohistochemistry and Western blot. Results Pharmacologic depletion of B cells did not influence infarct volumes and functional outcome at day 1 after stroke. Additionally, lack of circulating B cells in JHD −/− mice also failed to influence stroke outcome at days 1 and 3. Furthermore, reconstitution of Rag1 −/− mice with B cells had no influence on infarct volumes. Conclusion Targeting B cells in experimental stroke did not influence lesion volume and functional outcome during the acute phase. Our findings argue against a major pathophysiologic role of B cells during acute ischemic stroke.
topic Ischemic stroke
Transient middle cerebral artery occlusion
B cells
url http://link.springer.com/article/10.1186/s12974-017-0890-x
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AT peterkraft bcellsdonothaveamajorpathophysiologicroleinacuteischemicstrokeinmice
AT christophkleinschnitz bcellsdonothaveamajorpathophysiologicroleinacuteischemicstrokeinmice
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