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H. S. HAIN, S. F. DAVIS, A. Hu, V.V. ISTOMIN, M. C. IWUNZE, P. LORELLO, S.A. MALEKIANI, E.V. SABATH, V. ALEXANDROV, T. HANANIA

Traumatic brain injury (TBI) affects over 1.5 million people per year in the United States. Falls and motor vehicle accidents are the leading cause. Apart from the initial damage, secondary, delayed brain damage occurs immediately after the initial insult. These secondary insults include edema, excitotoxicity, mitochondrial dysfunction hypoxia and ischemia (Mackintosh et al., 1996). The cost of TBI-related hospitalization, treatment, rehabilitation injury- related work loss, has been estimated to be 76.5 billion annually (CDC data). Progesterone is currently in Phase II clinical trials for TBI (Wright et al., 2007). In rats elevated progesterone levels has been shown to play a significant role in reducing tissue damage after injury and subsequently leading to a functional recovery (Stein et al., 1987). In this study we examined the behavioral effects of progesterone (4, 8 and 16 mg/kg administered 1 hour post injury followed by once daily for 5 days) on cognitive, and gait deficits induced by a bilateral controlled cortical impact injury (CCI) in Sprague Dawley rats. Rats with CCI exhibited a significant decrease in the number of spontaneous alternations compared to sham-injury rats when tested in a plus-shaped maze and an increase in the latency to reach the platform during acquisition in the Morris Water Maze (MWM) test. Treatment with progesterone (16 mg/kg) reversed the cognitive deficits seen in the injured rats in both tests. One week after injury gait dynamics and geometry were evaluated using NeuroCube™, PsychoGenics’ propriety technology for gait analysis. Significant differences in gait measures were found between CCI and Sham rats. Progesterone dose dependently recovered these gait deficits. The results of our study further support the possible use of Progesterone in management of TBI in clinics.