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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD040833-03
Application #
6645436
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Nitkin, Ralph M
Project Start
2001-09-01
Project End
2006-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
3
Fiscal Year
2003
Total Cost
$124,686
Indirect Cost
Name
University of Pittsburgh
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Wagner, Amy K; Sokoloski, Joshua E; Chen, Xiangbai et al. (2009) Controlled cortical impact injury influences methylphenidate-induced changes in striatal dopamine neurotransmission. J Neurochem 110:801-10
Wagner, Amy K; Drewencki, Laura L; Chen, Xiangbai et al. (2009) Chronic methylphenidate treatment enhances striatal dopamine neurotransmission after experimental traumatic brain injury. J Neurochem 108:986-97
Majerske, Cynthia W; Mihalik, Jason P; Ren, Dianxu et al. (2008) Concussion in sports: postconcussive activity levels, symptoms, and neurocognitive performance. J Athl Train 43:265-74
Wagner, Amy K; Kline, Anthony E; Ren, Dianxu et al. (2007) Gender associations with chronic methylphenidate treatment and behavioral performance following experimental traumatic brain injury. Behav Brain Res 181:200-9
Wagner, Amy K; Postal, Brett A; Darrah, Shaun D et al. (2007) Deficits in novelty exploration after controlled cortical impact. J Neurotrauma 24:1308-20
Wagner, Amy K; Ren, Dianxu; Conley, Yvette P et al. (2007) Sex and genetic associations with cerebrospinal fluid dopamine and metabolite production after severe traumatic brain injury. J Neurosurg 106:538-47
Wagner, Amy K; Fabio, Anthony; Puccio, Ava M et al. (2005) Gender associations with cerebrospinal fluid glutamate and lactate/pyruvate levels after severe traumatic brain injury. Crit Care Med 33:407-13
Wagner, A K; Sokoloski, J E; Ren, D et al. (2005) Controlled cortical impact injury affects dopaminergic transmission in the rat striatum. J Neurochem 95:457-65
Wagner, Amy K; Chen, Xiangbai; Kline, Anthony E et al. (2005) Gender and environmental enrichment impact dopamine transporter expression after experimental traumatic brain injury. Exp Neurol 195:475-83
Chen, X; Li, Y; Kline, A E et al. (2005) Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury. Neuroscience 135:11-7

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