HEAD INJURY CLINICAL RESEARCH CENTER

这项赠款申请寻求继续资助头部受伤 宾夕法尼亚大学的研究中心，一个中心现在在其 存在的第23年。 在这段时间里，这项研究已经成为 创伤性轴索损伤（TRAUMATIC AXONAL DAMAGE，缩写为AXONAL）， 人类脑损伤的功能障碍，因此， 的中心。 在世界上超过一半的国家， 经病理学检查的致命伤， 轴突损伤（DAI），在三分之一的严重脑损伤的人。 到 为了更好地理解脑卒中的病理生理学，本申请提出 使用最先进的神经成像，光谱学，电子 显微镜、免疫组织化学和分子生物学方法 协调涉及五个项目的研究工作。 前两 项目利用磁共振转移成像（MTI）， 磁共振波谱（MRS），以确定非侵入性的纵向变化， 创伤性白色物质结构与生物化学 在实验DAI和人类的异常，分别，将 联合收割机将这些方法结合起来进行临床诊断。 第三个项目 表征立即早期基因（IEG）表达的变化， 模型中的应激蛋白、IEGs的靶基因和神经递质 为了确定基因组变化对 对伤害的反应。 第四个项目使用的实验模型的 为了确定靶向于以下的新型神经保护化合物的功效， 受体或细胞骨架功能障碍。 两个基本 核心活动支持这些项目。 核心A提供行政 活动、生物统计支持、患者数据库维护和 评价新的成果工具。 核心B提供生物工程支持， 设计改进的模型，在复制人脑方面具有更高的保真度 损伤，并量化实验模型之间的关系， 人体伤害。 这些研究将进一步加深我们对 脑损伤的病理生理学，并将导致新的发展 以及用于治疗脑损伤患者的改进的疗法。

This grant application seeks continued funding for the Head Injury Research Center at the University of Pennsylvania, a Center now in its 23rd year of existence. During that time, the research has become focused on TRAUMATIC AXONAL DAMAGE (TAD), an important focus of dysfunction in human brain injury, and, thus, TAD is the overall theme of the Center. TAD occurs in various forms in well over half of all fatal injuries examined pathologically and in a pure form, as diffuse axonal injury (DAI), in one-third of severely brain injured humans. To understand the pathophysiology of TAD better, this application proposes the use of state-of-the-art neuroimaging, spectroscopy, electron microscopy, immunohistochemical and molecular biologic methods in a coordinated research effort involving five projects. The first two projects utilize magnetic resonance transfer imaging (MTI) and spectroscopy (MRS) to determine non-invasively longitudinal changes in structure and in-vivo biochemistry of traumatic white matter abnormalities in experimental DAI and humans, respectively, and will combine these into methods to diagnose TAD clinically. A third project characterizes changes in expression of immediate early genes (IEG), stress proteins, target genes of the IEGs and neurotransmitters in models of TAD in order to determine the influence of genomic changes on responses to injury. A fourth project uses experimental models of TAD to determine efficacy of novel neuroprotective compounds targeted at receptor or cytoskeletal dysfunction in mitigating TAD. Two essential core activities support the Projects. Core A provides administrative activities, biostatistical support, patient database maintenance and evaluation of new outcome tools. Core B provides bioengineering support, designs improved models with higher fidelity in replicating human brain injury, and quantifies the relationships between experimental models and human injuries. Theses studies will further our understanding of the pathophysiology of brain injury and will lead to the development of novel and improved therapies for the treatment of brain injured patients.