EXPLORING STRATEGIES TO IMPROVE OUTCOME AFTER REPEATED MILD BLAST TBI

TBI caused by explosive blast (blast traumatic brain injury; bTBI) has become a key military medical issue. During recent conflicts, approximately 70% of US military casualties were caused by explosive blast. Of the estimated 300,000 neuropsychiatric ¿casualties¿ from Operation Iraqi Freedom alone, approximately 50% suffered from repeated exposure to mild levels of explosive blast. Epidemiological studies have suggested that the effects of repeated blast overpressure exposure maybe cumulative. Conservative estimates put aggregate lifetime costs of treatment for bTBI victims at more than 600 BILLION dollars. This exploratory proposal tests the efficacy of an FDA approved drug, 2-methoxyestradiol (2ME2), which has been shown to prevent the development of chronic damage after neuronal insults like hypoxia. 2ME2 is safe, well tolerated, and has been extensively tested. The drug was identified based on experimental data, thus it offers one of the best chances to prevent the development of long-term problems in repeated mild bTBI (rmbTBI). If 2ME2 treatment mitigates the neurobehavioral consequences of multiple mild blast exposure in our experimental model, it can be tested in clinical trials on selected human populations.