Mechanisms and modifying factors of ischemic brain injur

缺血性脑损伤的机制及影响因素

• 批准号: 6671487
• 负责人: Alison E Baird
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6671487
• 关键词: brain imaging /visualization /scanning; brain injury; cerebral ischemia /hypoxia; cytokine; functional ability; gene expression; human subject; inflammation; lymphocyte; magnetic resonance imaging; monocyte; stroke

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 only 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. This work follows on from prior work showing the importance of perfusion changes on the evolution of ischemic lesions and on stroke recovery and the potential for delayed clinical recovery after stroke. These prior studies used serial brain imaging studies with single photon emission computed tomography and ultrafast high resolution magnetic resonance imaging. Our work is now focused on studying the effects of inflammation and genetic factors on ischemic lesion evolution and recovery, using detailed and serial clinical and neuroimaging information in conjunction with cytokine expression and genetic expression in peripheral blood mononuclear cells. Our aim is to determine if a "pro-inflammatory" state leads to a worse outcome after stroke. This information is of particular relevance with the report of a potential stroke vaccine which is targeted at reducing pro-inflammation after stroke, with a view to reducing stroke recurrence in experimental models. At present there is very limited information pertaining to clinical stroke. Our aim is to also determine if signatures of genetic expression profile in peripheral white blood cells can be identified that are associated with stroke recovery. Over the past year the cytokine expression of peripheral blood mononuclear cells has been studied in 105 stroke patients and correlated with clinical outcome. We are also correlating the cytokine expression with magnetic resonance imaging findings such as development of hemorrhagic transformation and the development of new ischemic lesions over time. Two abstracts have been accepted for presentation at the American Stroke Association conference in February 2002. We have also studied a novel subset of the T cell population, CD4+CD28- cells, and found elevated levels in stroke patients relative to controls, and elevated levels in stroke patients with poor outcome compared to those with good outcome. For the stroke genomics project, blood samples have been gathered from 27 patients to date and from 9 control subjects.

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，只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。卒中神经科学部的项目侧重于确定与缺血性脑损伤和卒中后恢复相关的机制和修正因素。这项工作是在先前工作的基础上进行的，显示了血流灌注变化对缺血性病变演变和卒中恢复的重要性，以及卒中后临床恢复延迟的可能性。这些先前的研究使用了一系列的脑成像研究，包括单光子发射计算机断层扫描和超快高分辨率磁共振成像。 我们的工作现在集中在研究炎症和遗传因素对缺血性病变演变和恢复的影响，使用详细和系列的临床和神经影像信息，并结合外周血单个核细胞中细胞因子的表达和基因表达。我们的目标是确定“促炎”状态是否会导致中风后更糟糕的结果。这一信息与一种潜在的中风疫苗的报告特别相关，该疫苗旨在减少中风后的促炎反应，以期在实验模型中减少中风的复发。目前，与临床卒中有关的信息非常有限。我们的目标也是确定是否可以识别外周血白细胞中与中风康复相关的基因表达谱特征。 在过去的一年里，对105例中风患者外周血单个核细胞细胞因子的表达进行了研究，并与临床结果进行了相关性研究。我们还将细胞因子的表达与磁共振成像结果相关联，例如随着时间的推移，出血性转化的发展和新的缺血性病变的发展。两篇摘要已被接受在2002年2月的美国中风协会会议上发表。我们还研究了一种新的T细胞亚群，即CD4+CD28-细胞，发现中风患者的水平高于对照组，而预后不良的中风患者的水平高于预后良好的患者。对于中风基因组学项目，到目前为止，已经从27名患者和9名对照受试者身上采集了血液样本。