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Phenotypic Changes in Immune Cell Subsets Reflect Increased Infarct Volume in Male vs. Female Mice

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Abstract

Inflammatory responses in the brain after cerebral ischemia have been studied extensively in male mice, but not female mice, thus potentially giving a less-than-accurate view of gender associated pathological processes. In humans, cerebral infarcts are typically smaller in premenopausal females than in age-matched males. In the current study, we confirmed smaller infarcts in female vs. male mice after middle cerebral artery occlusion and 96 h of reperfusion. Moreover, we explored immunological alterations related to this difference and found that the percentage of CD4+ T lymphocytes was significantly higher in spleens in males than females, with increased expression of the activation markers, CD69 and CD44. In contrast, the percentage of CD8+ T lymphocytes was significantly higher in spleens of females than males, leading to the identification of a small but distinct population of IL-10-secreting CD8+CD122+ suppressor T cells that were also increased in females. Finally, we observed that males have a greater percentage of activated macrophages/microglia in the brain than females, as well as increased expression of the VLA-4 adhesion molecule in both brain and spleen. This new information suggesting gender-dependent immunological mechanisms in stroke implies that effective treatments for human stroke may also be gender specific.

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Acknowledgments

The authors wish to thank Dr. Gil Benedek for the helpful discussions and Melissa Barber for the assistance in submitting the manuscript. This work was supported by NIH grant no. NS076013. 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.

Conflict of Interest

Anirban Banerjee declares that he has no conflict of interest.

Jianming Wang declares that he has no conflict of interest.

Sheetal Bodhankar declares that she has no conflict of interest.

Arthur A. Vandenbark declares that he has no conflict of interest.

Stephanie J. Murphy declares that she has no conflict of interest.

Halina Offner declares that she has no conflict of interest.

Compliance with Ethics Requirements

All institutional and national guidelines for the care and use of laboratory animals were followed. This article does not contain any studies with human subjects.

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Authors and Affiliations

  1. Neuroimmunology Research, Portland Veterans Affairs Medical Center, R&D-31, 3710 SW US Veterans Hospital Road, Portland, OR, USA

    Anirban Banerjee, Sheetal Bodhankar, Arthur A. Vandenbark & Halina Offner

  2. Department of Neurology, Oregon Health and Science University, Portland, OR, USA

    Anirban Banerjee, Sheetal Bodhankar, Arthur A. Vandenbark & Halina Offner

  3. Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA

    Jianming Wang, Stephanie J. Murphy & Halina Offner

  4. Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA

    Arthur A. Vandenbark

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  1. Anirban Banerjee
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  2. Jianming Wang
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  6. Halina Offner
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Correspondence to Halina Offner.

Additional information

Anirban Banerjee and Jianming Wang contributed equally to this work.

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Banerjee, A., Wang, J., Bodhankar, S. et al. Phenotypic Changes in Immune Cell Subsets Reflect Increased Infarct Volume in Male vs. Female Mice. Transl. Stroke Res. 4, 554–563 (2013). https://doi.org/10.1007/s12975-013-0268-z

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  • DOI: https://doi.org/10.1007/s12975-013-0268-z

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