Grant: Catalyst Grant - Mild Traumatic Brain Injury - Blast-Induced

In recent years, the increasing use of improvised explosive devices during the conflicts in Afghanistan and Iraq has resulted in an increase in mild-to-moderate traumatic brain injuries (mTBI) suffered by soldiers in combat areas. However, due to the complex nature of the injuries, treatment options are limited. Often soldiers exposed to minor blasts event, who initially exhibit no outward negative effects, sometimes develop memory and behavior changes days or months after the initial event. For these reasons, mTBI has become a major focus of casualty care. Our objectives are to achieve a better understanding of the biological mechanisms by which mTBI produces pathological changes to the brain, in order to drive the development of novel pharmacotherapies. Previous studies have revealed that one consequence of a traumatic blast injury is the abnormal release of an excitatory signaling molecule (glutamate) in the brain. This abnormal release can result in overstimulation of glutamate's normal receptors (known as excitotoxicty), and this can lead to the death and dysfunction of brain cells. We have previously developed a novel drug (GluR2-3Y) which has shown an ability to block the excitotoxic overstimulation of glutamate receptors in a cellular model of stroke, thereby reducing the death of brain cells. In our present study, we propose to study the biological changes that occur in the brain following mTBI, and test the ability of our drug to reduce the death and dysfunction of brain cells that occur following mTBI. We believe that our proposed study will provide critical information surrounding the biological changes that occur in the brain following mTBI, and if our GluR2-3Y drug shows a similar effect in mitigating the damage caused by mTBI as it does in a model of stroke, we believe that it may have the potential to drive the development of new therapeutics to treat these injuries and have a positive impact on the health of soldiers suffering from mTBI.