Mechanisms and modifying factors of ischemic brain injur

虽然中风是第三大死亡原因和成人残疾的主要原因，但目前只有一种经批准的中风疗法适用于一小部分患者。缺乏中风治疗的一个主要因素是缺乏中风病理生理学知识。中风神经科学部的项目重点是通过对人体外周血和组织样本的活体分析，确定与缺血性脑损伤和中风后恢复相关的机制和修饰因素。目前，该实验室正在探索(1)炎症和(2)遗传标记物对中风风险和预后的临床意义，最终目的是为新的治疗方法确定生物标记物和分子和遗传靶点。 在过去的一年里，已经发现了许多可以预测中风风险的炎性标志物，而一种新的T细胞亚群的增加被发现与中风复发和死亡显著相关。在妇女健康倡议中，C-反应蛋白、e-选择素、总白细胞计数和白细胞介素6升高是中风的预测因素。与哈佛大学公共卫生学院的研究人员合作进行的一项荟萃分析发现，牙周病可以预测中风风险。在我们的实验室中，已经发现了一种新的中风复发和死亡的标志物：T细胞亚群CD4CD28-的克隆性增殖。在根据年龄、中风严重程度和既往中风病史进行调整后，这些细胞水平的升高与一年内中风复发和/或死亡的风险增加2.5倍相关。这些细胞可能成为预防中风复发和死亡的生物标志物和潜在的治疗靶点。我们还从培养中刺激的外周血单核细胞中鉴定出一些细胞因子，患者的单核细胞和中性粒细胞在卒中发病后早期就被激活(肿瘤坏死因子和白介素8)。 在(2)卒中基因组学研究中，分析了20名患者和20名对照组的外周血单个核细胞的基因表达谱，发现了113个在患者和对照组之间存在显著差异的基因。由10名患者和10名对照组成的独立系列的验证研究正在进行中。初步结果显示，训练数据集在患者和对照组之间显示出良好的区分性。研究正在进行中，并正在扩展到与中风康复相关的基因组图谱。

While stroke is the third leading cause of death and the leading cause of adult disability, there is only one approved stroke therapy at present that reaches a small percentage of patients. One major factor for the lack of stroke treatments is the lack of knowledge about stroke pathophysiology. The projects of the Stroke Neuroscience Unit are focused on determining the mechanisms and modifying factors associated with ischemic brain injury and with recovery after stroke, by the in vivo analysis of human peripheral blood and tissue samples. Currently the laboratory is exploring the clinical significance of (1) inflammatory and (2) genetic markers on stroke risk and outcome, the ultimate aim being to identify biomarkers and molecular and genetic targets for novel therapies. Over the past year, a number of (1) inflammatory markers have been identified that are predictive of stroke risk, while an increase in a novel T cell subset has been found to be significantly associated with stroke recurrence and death. In the Women's Health Initiative, elevated C-reactive protein, e-selectin, total white blood cell count and interleukin-6 were predictive of stroke. Periodontal disease was found to be predictive of stroke risk in a meta-analysis performed in collaboration with investigators at the Harvard School of Public Health. In our lab, a novel marker for stroke recurrence and death has been identified: clonal expansion of a T cell subset, CD4+CD28-. Elevated levels of these cells are associated with a 2.5 times greater risk of stroke recurrence and/or death at one year, after adjustment for age, stroke severity and a history of prior stroke. These cells may serve as a biomarker and potential therapeutic target for preventing stroke recurrence and death. We have also identified a number of cytokines from peripheral blood mononuclear cells stimulated in culture that are elevated in patients relative to controls, suggesting activation of monocytes and neutrophils early after stroke onset (tumor necrosis factor and interleukin-8). In the (2) stroke genomics studies, the gene expression profile of peripheral blood mononuclear cells from 20 patients and 20 controls has been analyzed and 113 genes have been identified that are significantly different between patients and controls. Validation studies are in progress in an independent series of 10 patients and 10 controls. Initial results are showing that the training dataset shows good discrimination between patients and controls. Studies are ongoing and being extended to the genomic profile associated with stroke recovery.