Dopamine Function in TBI--Therapeutic Intervention

描述(申请人提供)：TBI是美国的一种流行病 幸存者往往有几十年的生产寿命损失。据估计 530万美国人，或总人口的2%，目前与 脑损伤导致的残疾。额叶综合征是一种 伴有额叶皮质的脑外伤患者认知功能障碍的临床特征 批判性地参与执行认知功能，包括 目标导向的行为，认知活动的启动和动机， 以及新的和应用学习的策略。虽然有人怀疑 前额叶皮质中的DA在工作记忆和其他 关于执行功能的各个方面，人们对DA的确切作用知之甚少 额叶皮质通路介导了脑外伤后的认知障碍。正在进行中 研究工作开始研究中皮质的细胞机制 多巴胺能缺陷在啮齿动物损伤模型中的作用 药物疗法正在研究中。然而，在文献中有一个空白 突触前DA神经传递的体内动力学特性研究 损伤后，其在认知障碍中的作用，以及对特定的反应 药物治疗和环境刺激。此应用程序的目标是 是研究大脑皮层DA的时间特征 脑外伤啮齿动物模型中的神经传递动力学。这些发现将是 多巴胺神经传递和神经行为组织标志物的比较 性能。丰富的环境和DA增强的效果 对该系统的药物治疗也将进行研究。这项研究计划 研究将为以下人员提供职业发展的框架和环境 首席调查员将成为独立调查员研究 颅脑损伤后的损伤和恢复机制。首席调查员将 参与课程作业，掌握基本的科学实验技能 与拟议的研究计划相关。物理医学系 康复、神经外科、麻醉/重症监护医学和SAFAR 复苏研究中心为这项研究提供环境 实验性和临床性脑损伤。

DESCRIPTION (provided by applicant): TBI is an epidemic in the United States with survivors often having many decades of productive life loss. An estimated 5.3 million Americans, or 2 percent of the population, currently live with disabilities resulting from brain injury. Frontal lobe syndrome is one of the clinical hallmarks of cognitive dysfunction in TBI, with the frontal cortex being critically involved with executive cognitive functioning that includes goal directed behaviors, initiation and motivation for cognitive activities, and strategies for new and applied learning. While it has been suspected that DA in the prefrontal cortex plays a crucial role in working memory and other aspects of executive functioning, little is known about the precise role of DA pathways in frontal cortex mediated cognitive deficits following TBI. Ongoing work is beginning to examine the cellular mechanisms of mesocortical dopaminergic deficits in a rodent injury model, and the role of specific pharmacotherapies is being studied. However, there is a gap in the literature examining the in vivo kinetic properties of presynaptic DA neurotransmission after injury, its role in cognitive deficits, and the response to specific pharmacotherapies and environmental stimulation. The goal of this application is to examine the temporal characteristics of mesocortical DA neurotransmission kinetics in a rodent TBI model. These findings will be compared to tissue markers of DA neurotransmission and neurobehavioral performance. The effects of an enriched environment and DA enhancing pharmacotherapy on this system will also be studied. This research plan of study will provide a framework and environment for career development for the Principal Investigator to become an independent investigator studying mechanisms of injury and recovery after TBI. The Principal Investigator will participate in coursework and acquire basic science laboratory skills pertinent to the proposed research plan. The Departments of Physical Medicine and Rehabilitation, Neurosurgery, Anesthesia/Critical Care Medicine, and Safar Center for Resuscitation Research provide the environment for this study of experimental and clinical brain injury.