This proposal is a competing renewal which aims to better understand why infection, which is common after stroke, negatively impacts outcome. Our research demonstrates that an immune response to central nervous system (CNS) antigens occurs after stroke and that the nature of this immune response depends upon the experimental conditions and affects neurological outcome. Specifically, Lewis rats that develop a TH1 type immune response to brain antigens experience worse outcome while Lewis rats that develop a regulatory type response (TREG) experience better outcome. The predisposition to developing a TH1 response is increased by systemic inflammation induced with lipopolysaccharide (LPS). We believe that this model may help to explain why patients who develop an infection following stroke experience worse outcome. The goals of the current project are to assess the """"""""clinical relevance"""""""" of our model by validating our findings using a true infection model. We further aim to better define the nature and regulation of this post-ischemic immune response and assess the effect of antibiotic therapy and the role of the sympathetic nervous system on this response. The primary hypothesis to be addressed in the research outlined is: does systemic infection in the immediate post-stroke period increase the likelihood of developing a detrimental autoimmune response to CNS antigens?

Public Health Relevance

Infection is common after stroke and is associated with worse outcome. It is possible that this detrimental effect is mediated by the development of an autoimmune response to brain, and as such, could be modulate to improve outcome.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Bosetti, Francesca
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University of Washington
Schools of Medicine
United States
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Zierath, Dannielle; Shen, Angela; Stults, Astiana et al. (2017) Splenectomy Does Not Improve Long-Term Outcome After Stroke. Stroke 48:497-500
Becker, Kyra J (2016) Strain-Related Differences in the Immune Response: Relevance to Human Stroke. Transl Stroke Res 7:303-12
Becker, Kyra J; Zierath, Dannielle; Kunze, Allison et al. (2016) The contribution of antibiotics, pneumonia and the immune response to stroke outcome. J Neuroimmunol 295-296:68-74
Zierath, Dannielle; Kunze, Allison; Fecteau, Leia et al. (2015) Effect of Antibiotic Class on Stroke Outcome. Stroke 46:2287-92
Zierath, Dannielle; Kunze, Allison; Fecteau, Leia et al. (2015) Promiscuity of autoimmune responses to MBP after stroke. J Neuroimmunol 285:101-5
Zierath, Dannielle; Schulze, Juliane; Kunze, Allison et al. (2013) The immunologic profile of adoptively transferred lymphocytes influences stroke outcome of recipients. J Neuroimmunol 263:28-34
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
Savos, Anna V; Gee, J Michael; Zierath, Dannielle et al. (2011) ýý-MSH: a potential neuroprotective and immunomodulatory agent for the treatment of stroke. J Cereb Blood Flow Metab 31:606-13
Zierath, Dannielle; Thullbery, Matthew; Hadwin, Jessica et al. (2010) CNS immune responses following experimental stroke. Neurocrit Care 12:274-84

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