The Contribution of Inflammation to Brain Injury after Stroke

描述(申请人提供)：中风是美国第三大死因。每年约有70万美国人中风(美国心脏协会[AHA]，2006)；其中88%是缺血性中风(AHA，2006)。那些能够从缺血性中风中恢复和康复的人往往会留下需要支持性护理的长期残疾，并面临更多疾病和伤害(AHA)的风险。已知缺血性卒中和再灌流后炎症反应增强。这些反应增加了脑损伤(Crack&Taylor，2005；D‘Ambrosio等人，2001；Ritter等人，2000；Ritter等人，2005；Ruehl等人，2002)。我们也知道，白细胞激活是导致中风后脑损伤的一种炎症机制。然而，其他炎症介质对白细胞激活和随后的脑损伤的影响尚不清楚。为了解决这一认识上的差距，这项研究的总体目标是确定新的炎性补充蛋白如何在中风后白细胞介导的脑损伤中发挥作用。将使用不表达补体蛋白甘露糖结合凝集素补体的转基因小鼠模型进行定量实验设计。根据缺血性中风和再灌注的外科方法，将进行行为分析、用组织染色方法测量梗死面积，以及血液炎症标志物的生化分析。申请者和导师是完美匹配的，研究环境有力地支持了申请者的研究培训计划。申请者的导师莱斯利·里特博士已经制定了与炎症和中风机制相关的研究计划。她拥有一个实验室，一个强大的跨学科研究团队，并曾指导过成功的博士生。这项研究与公共卫生的相关性：拟议的具体研究项目的成果将填补与了解导致中风后脑损伤的特定炎症机制相关的知识空白，从而为每年70万中风患者服务。随后，这种对科学的贡献将转化为新的中风疗法的开发，这些疗法将限制脑损伤，延长健康寿命，并减少缺血性中风造成的残疾。拟议的研究培训计划的结果将是培养一名护士科学家，在她的职业生涯中，她将继续为了解缺血性中风炎症过程和护理经历过这种脑损伤的人做出重大贡献

DESCRIPTION (provided by applicant): Stroke is the third leading cause of death in the US. About 700,000 Americans have a stroke each year (American Heart Association [AHA], 2006); 88% of these are ischemic strokes (AHA, 2006). Those able to recover and rehabilitate from ischemic stroke are often left with long-term disabilities requiring supportive care and are at increased risk for further illness and injury (AHA). It is known that inflammatory responses are increased after ischemic stroke and reperfusion. These responses increase brain injury (Crack & Taylor, 2005; D'Ambrosio et al., 2001; Ritter et al., 2000; Ritter et al., 2005; Ruehl et al., 2002). It is also known that leukocyte activation is one inflammatory mechanism that contributes to brain injury after stroke. However, the influence of other inflammatory mediators on leukocyte activation, and subsequent brain injury, remains unclear. To address this gap in knowledge, the overall goal of this research is to determine how novel inflammatory complement proteins contribute to leukocyte mediated brain injury after stroke. A quantitative experimental design using a transgenic mouse model, that does not express the complement protein mannose binding lectin complement, will be employed. Following a surgical method of ischemic stroke and reperfusion, behavioral analysis, measurement of infarct area using tissue staining methods, and biochemical analyses of blood markers of inflammation will be performed. The applicant and mentor are perfectly matched and the research environment strongly supports the applicant's research training plan. Dr. Leslie Ritter, the applicant's mentor, has an established program of research related to mechanisms of inflammation and stroke. She maintains a laboratory, a strong interdisciplinary research team, and has mentored successful doctoral students. Relevance of this research to public health: The outcomes of the specific proposed research project will serve the 700,000 people who suffer a stroke each year, by filling a gap in knowledge related to the understanding of the specific inflammatory mechanisms that contribute to brain injury after stroke. Subsequently, this contribution to science will translate into the development of new stroke therapies that will limit brain injury, extend healthy life, and reduce disability from ischemic stroke. The outcome of the proposed research training plan will be to prepare a nurse scientist who, over the course of her career, will continue to make significant contributions to the understanding of the ischemic stroke inflammatory process and the care of people who experience this kind of brain injury