Abstract

The hypotheses to be tested in this proposal are that the post-ischemic immune response contributes to brain injury and that brain injury can be reduced by appropriately modulating the immune response. Soon after the onset of ischemic stroke, lymphocytes infiltrate the brain and an immune response is triggered against brain antigens. Using an animal model of transient middle cerebral artery occlusion, we will define the nature of the post-ischemic immune response and explore ways to manipulate that response for therapeutic benefit.
The specific aims of the project are: 1) to determine the time between ischemic stroke onset and development of a cellular immune response directed towards brain antigens, and to analyze that response, 2) to determine the nature and time course of lymphocyte infiltration into brain after stroke, and 3) to define the therapeutic potential of modulating the post-ischemic cellular immune response.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02NS002160-04
Application #
6639329
Study Section
NST-2 Subcommittee (NST)
Program Officer
Jacobs, Tom P
Project Start
2000-04-05
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
4
Fiscal Year
2003
Total Cost
$102,319
Indirect Cost

  Institution

Name
University of Washington
Department
Neurology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Becker, Kyra (2012) Autoimmune responses to brain following stroke. Transl Stroke Res 3:310-7
Becker, Kyra J (2012) Activation of immune responses to brain antigens after stroke. J Neurochem 123 Suppl 2:148-55
Dirnagl, Ulrich; Becker, Kyra; Meisel, Andreas (2009) Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol 8:398-412
Becker, K J (2009) Sensitization and tolerization to brain antigens in stroke. Neuroscience 158:1090-7
Gee, J Michael; Kalil, Angela; Thullbery, Matthew et al. (2008) Induction of immunologic tolerance to myelin basic protein prevents central nervous system autoimmunity and improves outcome after stroke. Stroke 39:1575-82
Gee, J Michael; Kalil, Angela; Shea, Connor et al. (2007) Lymphocytes: potential mediators of postischemic injury and neuroprotection. Stroke 38:783-8
Czartoski, T; Hallam, D; Lacy, J M et al. (2005) Postinfectious vasculopathy with evolution to moyamoya syndrome. J Neurol Neurosurg Psychiatry 76:256-9
Becker, Kyra J; Kindrick, Darin L; Lester, Mark P et al. (2005) Sensitization to brain antigens after stroke is augmented by lipopolysaccharide. J Cereb Blood Flow Metab 25:1634-44
Uchino, Ken; Johnston, S Claiborne; Becker, Kyra J et al. (2005) Moyamoya disease in Washington State and California. Neurology 65:956-8
Becker, Kyra; Skalabrin, Elaine; Hallam, Danial et al. (2004) Ischemic stroke during sexual intercourse: a report of 4 cases in persons with patent foramen ovale. Arch Neurol 61:1114-6

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