Annually, approximately 2 million Americans suffer a moderate to severe traumatic brain injury (TBI). These injuries produce enduring disabilities that include cognitive, sensory, motor, and emotional impairments. The associated health care costs from these injuries are staggering. Confounding this major public health issue is the fact that currently there are very few pharmacological treatment options for patients who have suffered TBI. In part, this occurs because many newly synthesized drugs fail in various stages of efficacy testing. Given the fact that newly synthesized drugs fail in clinical trials it seems reasonable to begin to examine the potential efficacy of more natural substances. It has recently been demonstrated that administration of vitamin B3 (B3) following experimentally induced stroke reduces the size of the infarct and can improve behavioral outcome in rats. In addition, the preclinical efficacy of magnesium pharmacotherapy has been well established. The proposed research will investigate the potential preclinical efficacy of B3 to lessen the physiological consequences of brain injury and improve behavioral outcome. We will use the rodent bilateral frontal cortical contusion injury model, which is similar to a frontal head injury sustained in a car accident.
The specific aims of this study are to: 1) determine if administration of B3 following injury can significantly reduce the cognitive and sensorimotor impairments seen following TBI; 2) determine the best injections parameters (i.e., window of opportunity and dose response) for B3 pharmacotherapy following TBI; 3) determine if administration of B3 following injury can significantly decrease the amount of injury-induced edema and injury-induced magnesium depletion; 4) determine the effect of B3 pharmacotherapy on apoptosis and reactive gliosis following TBI. The research proposed here will determine if B3 holds any preclinical efficacy for the treatment of TBI and begin to define the parameters for the development of B3 as a clinical treatment for TBI. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
7R15NS045647-02
Application #
6992626
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (01))
Program Officer
Hicks, Ramona R
Project Start
2004-09-01
Project End
2005-12-31
Budget Start
2004-09-01
Budget End
2005-12-31
Support Year
2
Fiscal Year
2003
Total Cost
$74,595
Indirect Cost
Name
Southern Illinois University Carbondale
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
939007555
City
Carbondale
State
IL
Country
United States
Zip Code
62901
Vonder Haar, Cole; Peterson, Todd C; Martens, Kris M et al. (2016) Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies. Brain Res 1640:114-129
Vonder Haar, Cole; Smith, Travis R; French, Eric J et al. (2014) Simple tone discriminations are disrupted following experimental frontal traumatic brain injury in rats. Brain Inj 28:235-43
Martens, Kris M; Vonder Haar, Cole; Hutsell, Blake A et al. (2013) The dig task: a simple scent discrimination reveals deficits following frontal brain damage. J Vis Exp :
Vonder Haar, Cole; Emery, Michael A; Hoane, Michael R (2012) Chronic folic acid administration confers no treatment effects in either a high or low dose following unilateral controlled cortical impact injury in the rat. Restor Neurol Neurosci 30:291-302
Hoane, Michael R; Swan, Alicia A; Heck, Sarah E (2011) The effects of a high-fat sucrose diet on functional outcome following cortical contusion injury in the rat. Behav Brain Res 223:119-24
Swan, Alicia A; Chandrashekar, Rupa; Beare, Jason et al. (2011) Preclinical efficacy testing in middle-aged rats: nicotinamide, a novel neuroprotectant, demonstrates diminished preclinical efficacy after controlled cortical impact. J Neurotrauma 28:431-40
Vonder Haar, Cole; Anderson, Gail D; Hoane, Michael R (2011) Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury. Behav Brain Res 224:311-7
Goffus, Andrea M; Anderson, Gail D; Hoane, Michael (2010) Sustained delivery of nicotinamide limits cortical injury and improves functional recovery following traumatic brain injury. Oxid Med Cell Longev 3:145-52
Kuypers, Nicholas J; Hoane, Michael R (2010) Pyridoxine administration improves behavioral and anatomical outcome after unilateral contusion injury in the rat. J Neurotrauma 27:1275-82
Quigley, Andrea; Tan, Arlene A; Hoane, Michael R (2009) The effects of hypertonic saline and nicotinamide on sensorimotor and cognitive function following cortical contusion injury in the rat. Brain Res 1304:138-48

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