Concussive brain injury is estimated to affect more than 500,000 Americans each year. The long-term results are often tragic both for the victim and for the family. In addition to mortality, the brain injury may result in the loss or substantial impairment of motor, sensory, and/or cognitive function. At the present time there are no effective treatment regimens that reliably and significantly improve the outcome following concussive brain injury. Until recently, it was commonly held that the brain was not able to recover from traumatic damage. Studies with methylprednisolone have demonstrated that early treatment following spinal cord trauma may significantly improve the clinical outcome. While no such treatment currently exists for brain trauma, it is now accepted that there is a series of early biochemical changes that occur within the first few minutes to hours. However, defining the window of opportunity to treat has not been possible in the past. We postulate that these early changes predispose the brain to secondary ischemic injury following trauma. This project is designed to characterize and modify the early and late cellular changes leading to secondary injury. We will demonstrate the time course for the early production free-radicals, leukotrienes, specific mRNAs, and oxidized proteins following concussive injury. Changes in enzymatic activity of marker enzymes (glutamine synthetase and ornithine decarboxylase) will be determined at different times following brain trauma. In addition, we will define the anatomic distribution of these changes in cellular function using histochemical staining for free-radical production, in inhibition of leukotriene synthesis, an inhibition of ornithine decarboxylase will be use as tools to understand the potential roles of each of these processes in the early changes following brain trauma. In addition, the effect of administration of insulin-like growth factor (IGF) on the post-concussive outcome measures described above will be determined. Once characterized, the parametric evaluation of the post-traumatic period with respect to intervention with free radical scavengers and growth factor will begin to describe the therapeutic window in the treatment of brain trauma.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Kentucky
United States
Zip Code
Gebregziabher, Mulugeta; Hoel, David (2009) Applications of the Poly-K Statistical Test to Life-Time Cancer Bioassay Studies. Hum Ecol Risk Assess 15:858-875
Hatton, Jimmi; Kryscio, Richard; Ryan, Melody et al. (2006) Systemic metabolic effects of combined insulin-like growth factor-I and growth hormone therapy in patients who have sustained acute traumatic brain injury. J Neurosurg 105:843-52
Scheff, S W; Price, D A; Hicks, R R et al. (2005) Synaptogenesis in the hippocampal CA1 field following traumatic brain injury. J Neurotrauma 22:719-32
Sullivan, Patrick G; Rabchevsky, Alexander G; Keller, Jeffery N et al. (2004) Intrinsic differences in brain and spinal cord mitochondria: Implication for therapeutic interventions. J Comp Neurol 474:524-34
Dempsey, Robert J; Raghavendra Rao, Vemuganti L (2003) Cytidinediphosphocholine treatment to decrease traumatic brain injury-induced hippocampal neuronal death, cortical contusion volume, and neurological dysfunction in rats. J Neurosurg 98:867-73
Raghavendra Rao, Vemuganti L; Bowen, Kellie K; Dhodda, Vinay K et al. (2002) Gene expression analysis of spontaneously hypertensive rat cerebral cortex following transient focal cerebral ischemia. J Neurochem 83:1072-86
Guo, Jun-Tao; Yu, Jin; Grass, David et al. (2002) Inflammation-dependent cerebral deposition of serum amyloid a protein in a mouse model of amyloidosis. J Neurosci 22:5900-9
Adibhatla, Rao Muralikrishna; Hatcher, James F; Sailor, Kurt et al. (2002) Polyamines and central nervous system injury: spermine and spermidine decrease following transient focal cerebral ischemia in spontaneously hypertensive rats. Brain Res 938:81-6
Rao, V L; Dogan, A; Bowen, K K et al. (2001) Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain. Eur J Neurosci 13:119-28
Rao, V L; Bowen, K K; Rao, A M et al. (2001) Up-regulation of the peripheral-type benzodiazepine receptor expression and [(3)H]PK11195 binding in gerbil hippocampus after transient forebrain ischemia. J Neurosci Res 64:493-500

Showing the most recent 10 out of 68 publications