Mechanisms and modifying factors of ischemic brain injur

虽然中风是导致死亡的第三大原因，也是导致成人残疾的主要原因，但目前只有一种经批准的中风治疗方法，仅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对中风病理生理学的了解。脑卒中神经科学部门的项目重点是确定缺血性脑损伤和脑卒中后恢复相关的机制和调节因素。这项工作是在先前的工作基础上进行的，表明灌注变化对缺血性病变的演变和卒中恢复的重要性，以及卒中后延迟临床恢复的潜力。这些先前的研究使用了单光子发射计算机断层扫描和超快高分辨率磁共振成像的连续脑成像研究。

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.