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Myelin specific cells infiltrate MCAO lesions and exacerbate stroke severity

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Abstract

Although inflammatory responses increase stroke severity, the role of immune cells specific for central nervous system (CNS) antigens remains controversial. Disruption of the blood–brain barrier (BBB) during stroke allows CNS antigens to leak into the peripheral circulation and enhances access of circulating leukocytes to the brain, including those specific for CNS antigens such as myelin oligodendrocyte glycoprotein (MOG) that can induce experimental autoimmune encephalomyelitis (EAE). We here demonstrate for the first time that myelin reactive splenocytes specific for MOG transferred into severe combined immunodeficient (SCID) mice can migrate into the infarct hemisphere of recipients subjected to 60 min middle cerebral artery occlusion (MCAO) and 96 h reperfusion; moreover these cells exacerbate infarct volume and worsen neurological deficits compared to animals transferred with naïve splenocytes. These findings indicate that autoimmunity in the CNS can exert detrimental injury on brain cells and worsen the damage from ischemic stroke.

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Acknowledgements

We thank Dr. Heng Hu, Dr. Sushmita Sinha, Dr. Sheetal Bodhankar, Dr. Suzan Dziennis, Dr. Takeru Shimizu and Ms. Sandhya Subramanian for helpful discussions; Ms. Xiao Jing Nie for performing histological staining and Ms. Lisa Miller for help with experiments; and Ms. Eva Niehaus for assistance in preparing the manuscript. This work was supported by NIH Grants NR03521 (PDH), NS49210 (PDH) and the Collins Medical Trust (XR). 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 statement

The authors have no financial conflicts of interest.

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Author notes

  1. Kozaburo Akiyoshi

    Present address: Department of Anesthesiology and Critical Care Medicine, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

Authors and Affiliations

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

    Xuefang Ren, Kozaburo Akiyoshi, Marjorie R. Grafe, Paco S. Herson & Halina Offner

  2. Neuroimmunology Research, R&D31, Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR, 97239, USA

    Xuefang Ren, Arthur A. Vandenbark & Halina Offner

  3. Department of Pathology, Oregon Health and Science University, Portland, OR, USA

    Marjorie R. Grafe

  4. Department of Veterans Affairs Medical Center, Sr. Research Career Scientist, Research Service, Portland, OR, USA

    Arthur A. Vandenbark

  5. Department of Neurology, Oregon Health & Science University, Portland, OR, USA

    Arthur A. Vandenbark & Halina Offner

  6. Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA

    Arthur A. Vandenbark

  7. Office of Health Affairs, The University of Texas System, Austin, TX, USA

    Patricia D. Hurn

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  1. Xuefang Ren
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Correspondence to Halina Offner.

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Ren, X., Akiyoshi, K., Grafe, M.R. et al. Myelin specific cells infiltrate MCAO lesions and exacerbate stroke severity. Metab Brain Dis 27, 7–15 (2012). https://doi.org/10.1007/s11011-011-9267-5

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  • DOI: https://doi.org/10.1007/s11011-011-9267-5

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