Intrastriatal B-cell administration limits infarct size after stroke in B-cell deficient mice (original) (raw)

Abstract

Recent evidence emphasizes B-cells as a major regulatory cell type that plays an important role in limiting the pathogenic effects of ischemic stroke. The aim of the current study was to extend this initial observation to specifically examine the infiltration of regulatory B-cells and to determine if the effect of B-cells to limit the inflammatory response to cerebral ischemia is mediated by their action centrally or peripherally. Our data demonstrate the increased presence of a regulatory B-cell subset in the affected hemisphere of wild-type mice after middle cerebral artery occlusion (MCAO). We further explored the use of a novel method of stereotaxic cell delivery to bypass the blood brain barrier (BBB) and introduce CD19+ B-cells directly into the striatum as compared to peripheral administration of B-cells. Infarct volumes after 60 minutes of MCAO and 48 hours of reperfusion were determined in B-cell deficient μMT−/− mice with and without replacement of either B-cells or medium. Infarct size was significantly decreased in cerebral cortex after intrastriatal transfer of 100,000 B-cells to μMT−/− mice vs. controls, with a comparable effect on infarct size as obtained by 50 million B-cells transferred intraperitoneally. These findings support the hypothesis that B-cells play a protective role against ischemic brain injury, and suggest that B-cells may serve as a novel therapeutic agent for modulating the immune response in central nervous system inflammation after stroke.

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Acknowledgments

The authors wish to thank Drs. Xuefang Ren, Wenri Zhang and Kozaburo Akiyoshi for assistance in some experiments, Ms. Eva Niehaus for assistance with manuscript preparation and Ms. Zefora Alderman for graphics. This work was supported by NIH grant NS075887. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.

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Authors and Affiliations

1. Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA
   Yingxin Chen, Stephanie J. Murphy, Nabil J. Alkayed & Halina Offner
2. Neuroimmunology Research R&D-31, Portland Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA
   Sheetal Bodhankar, Arthur A. Vandenbark & Halina Offner
3. Department of Neurology, Oregon Health & Science University, Portland, OR, USA
   Sheetal Bodhankar, Arthur A. Vandenbark & Halina Offner
4. Research Service, Department of Veterans Affairs Medical Center, Portland, OR, 97239, USA
   Arthur A. Vandenbark
5. Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA
   Arthur A. Vandenbark

Authors

1. Yingxin Chen
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2. Sheetal Bodhankar
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3. Stephanie J. Murphy
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4. Arthur A. Vandenbark
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5. Nabil J. Alkayed
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6. Halina Offner
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Corresponding author

Correspondence toHalina Offner.

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Yingxin Chen and Sheetal Bodhankar contributed equally to this work

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Chen, Y., Bodhankar, S., Murphy, S.J. et al. Intrastriatal B-cell administration limits infarct size after stroke in B-cell deficient mice.Metab Brain Dis 27, 487–493 (2012). https://doi.org/10.1007/s11011-012-9317-7

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• Received: 30 April 2012
• Accepted: 08 May 2012
• Published: 18 May 2012
• Issue Date: December 2012
• DOI: https://doi.org/10.1007/s11011-012-9317-7

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