Traumatic brain injury (TBI) is associated with a long-lasting decrement in the capacity of the brain to cope with future insults, and often with a reduced ability of individuals to maintain higher cognitive and intellectual function. It is likely that the capacity of the brain to remain functional following TBI depends upon a suitable environment for plasticity and the ability of cells to maintain synaptic transmission. In particular, oxidative stress (OS) as a primary event in the pathobiology of TBI has the power to deteriorate synaptic plasticity. This would compromise the capacity of cells to process, transmit, and store information, and ultimately disrupt higher order functions such as learning and memory. We propose studies to evaluate the hypothesis that OS and synaptic function are interrelated events such that a proper balance in free radical formation can aid synaptic plasticity and cognitive function after TBI. Brain-derived neurotrophic factor (BDNF) has a critical action on synaptic function underlying learning and memory. Based on our new findings that OS affects BDNF production and function, we propose studies to overcome dysfunctional synaptic plasticity after TBI under homeostatic conditions, by maintaining a suitable balance between OS and BDNF. Physical activity is an intrinsic component during the management of TBI patients, and is becoming commonly used therapeutically to promote functional restoration following TBI. Encouraged by our findings that physical activity reduces free radical formation and induces BDNF in the brain, we propose that exercise can be employed to improve functional recovery after TBI. We would like to evaluate the capacity of exercise to create a suitable environment for plasticity that can boost functional restoration following TBI. To date most intervention procedures for TBI have been based on adding exogenous substances into the brain ignoring the intrinsic capacity of the brain for plasticity. A positive outcome of these studies would open a new line of therapeutic treatments for TBI patients by endogenous up-regulation of neurotrophins.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS050465-05
Application #
7623489
Study Section
Special Emphasis Panel (ZRG1-BDCN-A (02))
Program Officer
Hicks, Ramona R
Project Start
2005-08-15
Project End
2010-08-14
Budget Start
2009-06-01
Budget End
2010-08-14
Support Year
5
Fiscal Year
2009
Total Cost
$345,655
Indirect Cost
Name
University of California Los Angeles
Department
Physiology
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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