We propose to investigate the mechanisms underlying brain dysfunction following traumatic brain injury (TBI) and to clarify recovery processes that may be targeted for therapeutic intervention. In Part 1 of this project, we propose to combine in vitro neurophysiological techniques with cognitive neurobehavioral assessment to evaluate the temporal course of alterations in hippocampal inhibitory circuitry after trauma and to document evidence for aberrant spatial and movement selective hippocampal cellular discharge. The strength of the relationship between cognitive behavior and these indices of hippocampal circuit dysfunction will clarify the role of the hippocampus in generating the functional deficits associated with TBI and whether hippocampal reorganization contributes to functional recovery. In Part 2, we will investigate the effects of TBI on hippocampal long-term potentiation (LTP) and long-term depression (LTD), using the hippocampal slice preparation. Experiments are proposed that will determine whether TBI-induced over activation of NMDA receptors in hippocampus mediates the suppression of LTP and whether NMDA receptor overactivation in vitro will mimic TBI-induced LTP suppression. In Part 3, we will use a newly developed three-dimensional autoradiographic imaging averaging method of expressing local glucose utilization combined with somatosensory circuit activation to quantitatively pinpoint areas of circuit reorganization after TBI. These functional data will be complemented by immunocytochemical and in situ hybridization studies to assess local alterations in pre- and postsynaptic markers and gene expression associated with circuit remodeling. Finally, slowly developing thalamic retrograde degeneration will be targeted for treatment using basic fibroblast growth factor in an attempt to protect somatosensory circuit structure and function. Together, these studies should contribute new information concerning the response of the nervous system to TBI as well as clarifying recovery mechanisms that may be targeted for therapeutic intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS030291-10
Application #
6455814
Study Section
Project Start
2001-06-01
Project End
2002-07-14
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
10
Fiscal Year
2001
Total Cost
$238,838
Indirect Cost
Name
University of Miami School of Medicine
Department
Type
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146
Dixon, Kirsty J; Turbic, Alisa; Turnley, Ann M et al. (2017) Explant Methodology for Analyzing Neuroblast Migration. Bio Protoc 7:
Dixon, Kirsty J; Mier, Jose; Gajavelli, Shyam et al. (2016) EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury. Stem Cell Res 17:504-513
Dietrich, W Dalton; Bramlett, Helen M (2016) Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation. Brain Res 1640:94-103
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Bramlett, Helen M; Dietrich, W Dalton (2015) Long-Term Consequences of Traumatic Brain Injury: Current Status of Potential Mechanisms of Injury and Neurological Outcomes. J Neurotrauma 32:1834-48
Blaya, Meghan O; Tsoulfas, Pantelis; Bramlett, Helen M et al. (2015) Neural progenitor cell transplantation promotes neuroprotection, enhances hippocampal neurogenesis, and improves cognitive outcomes after traumatic brain injury. Exp Neurol 264:67-81
Luo, Tianfei; Roman, Philip; Liu, Chunli et al. (2015) Upregulation of the GEF-H1 pathway after transient cerebral ischemia. Exp Neurol 263:306-13
Sun, Xin; Crawford, Robert; Liu, Chunli et al. (2015) Development-dependent regulation of molecular chaperones after hypoxia-ischemia. Neurobiol Dis 82:123-131
Dixon, Kirsty J; Theus, Michelle H; Nelersa, Claudiu M et al. (2015) Endogenous neural stem/progenitor cells stabilize the cortical microenvironment after traumatic brain injury. J Neurotrauma 32:753-64

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