Sensitization to Brain Antigens Following Stroke

描述（由申请人提供）：该提案是一项竞争性更新，旨在更好地理解为什么中风后常见的感染会对结果产生负面影响。我们的研究表明，对中枢神经系统（CNS）抗原的免疫反应发生在中风后，这种免疫反应的性质取决于实验条件和影响神经预后。具体来说，对脑抗原产生TH1型免疫反应的Lewis大鼠结果较差，而产生调节性反应（TREG）的Lewis大鼠结果较好。脂多糖（LPS）诱导的全身性炎症增加了TH1反应的易感性。我们相信这个模型可能有助于解释为什么中风后感染的患者会经历更糟糕的结果。当前项目的目标是通过使用真实的感染模型验证我们的发现来评估我们模型的“临床相关性”。我们进一步旨在更好地定义这种缺血后免疫反应的性质和调控，并评估抗生素治疗的效果和交感神经系统在这种反应中的作用。研究概述的主要假设是：中风后的全身性感染是否会增加对中枢神经系统抗原产生有害自身免疫反应的可能性？

DESCRIPTION (provided by applicant): 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?