Translational Research

Neurocritical Care

, Volume 12, Issue 2, pp 274-284

CNS Immune Responses Following Experimental Stroke

  • Dannielle ZierathAffiliated withDepartment of Neurology, University of Washington School of Medicine, Harborview Medical Center
  • , Matthew ThullberyAffiliated withDepartment of Neurology, University of Washington School of Medicine, Harborview Medical Center
  • , Jessica HadwinAffiliated withDepartment of Neurology, University of Washington School of Medicine, Harborview Medical Center
  • , J. Michael GeeAffiliated withDepartment of Neurology, University of Washington School of Medicine, Harborview Medical Center
  • , Anna SavosAffiliated withDepartment of Neurology, University of Washington School of Medicine, Harborview Medical Center
  • , Angela KalilAffiliated withDepartment of Neurology, University of Washington School of Medicine, Harborview Medical Center
  • , Kyra J. BeckerAffiliated withDepartment of Neurology, University of Washington School of Medicine, Harborview Medical Center Email author 

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Abstract

Background and purpose

Animals subjected to an inflammatory insult with lipopolysaccharide (LPS) at the time of stroke are predisposed to develop a detrimental autoimmune response to myelin basic protein (MBP). In this study, we sought to determine whether other inflammatory stimuli could similarly invoke central nervous system (CNS) autoimmunity and whether these detrimental autoimmune responses occurred to antigens other than MBP.

Methods

Male Lewis rats underwent 3 h middle cerebral artery occlusion (MCAO) and received intraperitoneal injections of LPS, staphylococcal enterotoxin B (SEB), lipoteichoic acid (LTA) or saline at the time of reperfusion. Behavioral tests were performed at set time intervals after MCAO and animals were sacrificed at 1 month to analyze the immune response to MBP, neuron specific enolase (NSE) and proteolipid protein (PLP).

Results

Lymphocytes from SEB treated animals were highly reactive to all tested CNS antigens, but treatment with LPS was most likely to lead to a Th1(+) response. A Th1(+) response to MBP, NSE or PLP in spleen was associated with worse outcome, although the response to NSE was most predictive of poor outcome. Animals with a cell mediated autoimmune response to either MBP or NSE in spleen had a concomitant humoral response to these antigens.

Conclusions

These data show that LPS, but not other inflammatory stimuli, increase the likelihood of developing a detrimental autoimmune response to an array of brain antigens.

Keywords

Stroke Toll-like receptor Autoimmune LPS LTA SEB MBP NSE PLP Th1 Fractalkine