Metabolic Brain Disease

, Volume 27, Issue 1, pp 7–15 | Cite as

Myelin specific cells infiltrate MCAO lesions and exacerbate stroke severity

  • Xuefang Ren
  • Kozaburo Akiyoshi
  • Marjorie R. Grafe
  • Arthur A. Vandenbark
  • Patricia D. Hurn
  • Paco S. Herson
  • Halina Offner
Original Paper

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.

Keywords

Experimental stroke Myelin reactive splenocytes Inflammatory responses Neurologic deficit 

Notes

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.

Supplementary material

11011_2011_9267_MOESM1_ESM.docx (255 kb)
ESM 1 (DOCX 254 kb)

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Xuefang Ren
    • 1
    • 2
  • Kozaburo Akiyoshi
    • 1
    • 8
  • Marjorie R. Grafe
    • 1
    • 3
  • Arthur A. Vandenbark
    • 2
    • 4
    • 5
    • 6
  • Patricia D. Hurn
    • 7
  • Paco S. Herson
    • 1
  • Halina Offner
    • 1
    • 2
    • 5
  1. 1.Department of Anesthesiology and Perioperative MedicineOregon Health & Science UniversityPortlandUSA
  2. 2.Neuroimmunology Research, R&D31Portland VA Medical CenterPortlandUSA
  3. 3.Department of PathologyOregon Health and Science UniversityPortlandUSA
  4. 4.Department of Veterans Affairs Medical CenterSr. Research Career Scientist, Research ServicePortlandUSA
  5. 5.Department of NeurologyOregon Health & Science UniversityPortlandUSA
  6. 6.Department of Molecular Microbiology & ImmunologyOregon Health & Science UniversityPortlandUSA
  7. 7.Office of Health AffairsThe University of Texas SystemAustinUSA
  8. 8.Department of Anesthesiology and Critical Care MedicineKyushu University HospitalFukuokaJapan

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