Grant: Operating Grant

Brain damage due to stroke and traumatic brain injury often has catastrophic consequences for patients and their families. Although current medical treatments have significantly improved the outcome of people who sustain these events, most individuals suffer lifetime impairments in bodily function and cognitive abilities. Thus, new therapies that can reduce the extent of damage to the brain following an injury and promote repair are greatly needed. A major contributor to brain damage following an injury is the neurotransmitter glutamate, which accumulates at sites of injury and is toxic to the surrounding cells. Hence, devising approaches to regulate glutamate and its receptors on neurons is important. The purpose of this grant is to identify and characterize new molecules that control the formation, stability, and strength of glutamate-based synaptic connections between neurons in the normal and injured brain. We have recently identified a new protein that is secreted by non-neuronal cells in the brain and plays a critical role in controlling the development and function of neural connections. Interestingly, the level of this protein is significantly increased at sites of brain injury. In this grant, we will utilize combined molecular, biochemical, imaging, behavioral and electrophysiological approaches to understand how this molecule regulates connections between neurons. These findings will help fuel proposed experiments which will directly investigate how this molecule regulates the function and health of neurons following brain injury. The ultimate goal is to reveal fundamental and new information that can improve the design and effectiveness of therapeutics that preserve the brain following an injury.