Dopamine Function in TBI--Therapeutic Intervention

描述（由申请人提供）：TBI在美国是一种流行病 幸存者往往有几十年的生产性生命损失。估计 5.3百万美国人，或2%的人口，目前生活在 脑损伤导致的残疾。额叶综合征是一种 脑外伤认知功能障碍的临床标志，额叶皮层 与执行认知功能密切相关，包括 目标导向行为，认知活动的启动和动机， 以及新的和应用的学习策略。虽然有人怀疑， 前额叶皮层中的DA在工作记忆和其他功能中起着至关重要的作用。 尽管我们对执行功能的各个方面都有研究，但我们对DA的确切作用知之甚少。 脑外伤后额叶皮层神经通路介导的认知功能障碍。正在进行 研究中皮层的细胞机制的工作已经开始 啮齿动物损伤模型中的多巴胺能缺陷，以及特异性 正在研究药物疗法。然而，在文献中存在空白 研究突触前DA神经传递的体内动力学特性 损伤后，其在认知缺陷中的作用，以及对特定 药物疗法和环境刺激。这个应用程序的目标是 是检查中皮层DA的时间特征 在啮齿动物TBI模型中的神经传递动力学。这些发现将是 与DA神经传递和神经行为的组织标志物相比， 性能丰富的环境和DA增强的影响 还将研究该系统的药物治疗。这项研究计划， 研究将为职业发展提供一个框架和环境， 主要研究者成为独立研究者 TBI后的损伤和恢复机制。主要研究者将 参加课程并获得基本的科学实验室技能 与拟议的研究计划有关。物理医学系 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了环境， 实验和临床脑损伤。

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.