Sensitization to Brain Antigens Following Stroke

中风后对脑抗原的敏感性

• 批准号: 8180463
• 负责人: KYRA J BECKER
• 金额: $ 30.62万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8180463
• 关键词: Address; Affect; Animals; Antibiotic Therapy; Antibiotics; Antigens; Attenuated; Autoimmune Responses; Brain; CNS autoimmunity; Clinical; Development; Fever; Goals; Gram-Negative Bacteria; Gram-Positive Bacteria; Immune response; Immunologics; Infection; Inflammation; Inflammatory Response; Lead; Lipopolysaccharides; Mediating; Modeling; Nature; Neuraxis; Neurological outcome; Outcome; Patients; Pneumonia; Predisposition; Rattus; Regulation; Research; Role; Severities; Simulate; Stroke; Sympathetic Nervous System; Systemic infection; Temperature; Testing; clinically relevant; experience; improved; post stroke; prevent; prognostic; response

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? 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.

描述(由申请人提供)：这项提案是一项竞争性的更新，旨在更好地了解为什么中风后常见的感染会对预后产生负面影响。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，并影响神经系统的结果。具体地说，对大脑抗原产生TH1型免疫反应的Lewis大鼠结局较差，而产生调节型反应(Treg)的Lewis大鼠结局较好。脂多糖(LPS)诱导的全身炎症增加了发生TH1反应的易感性。我们认为，这个模型可能有助于解释为什么中风后发生感染的患者预后更差。当前项目的目标是通过使用真实的感染模型来验证我们的发现，从而评估我们模型的“临床相关性”。我们的进一步目标是更好地确定这种缺血后免疫反应的性质和调节，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。在概述的研究中要解决的主要假设是：卒中后立即发生系统性感染是否会增加对中枢神经系统抗原产生有害的自身免疫反应的可能性？ 公共卫生相关性：中风后感染很常见，并与较差的预后相关。这种有害的影响可能是通过对大脑的自身免疫反应的发展来调节的，因此，可以通过调节来改善结果。