Dopamine Function in TBI--Therapeutic Intervention

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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.