Traumatic brain injury is a diverse and complex injury that affects 1.7 million Americans annually. Survivors frequently have permanent cognitive loss, behavioral issues, and emotional disturbances that affect them throughout their life. These life-altering changes are likely caused by damage to the cells of the brain that occur in response to injury. What remains unclear is how the behavior of brain cells is influenced by the events that occur during injury. To explore the response of brain cells to traumatic brain injury the research team has developed a novel bench top crash tester. Similar in concept to the full scale crash test systems used by the automotive industry, the bench top system will be used to apply impact conditions to populations of brain cells grown in the lab. The knowledge gained from this research program could help illuminate the poorly understood cellular changes that follow traumatic brain injuries and help guide the development of new therapies. The project will have broader impacts on neuroscience, biomedical engineering, and the healthcare field. The research will be complemented by integrated educational projects at the undergraduate and high school academic levels that are designed to motivate scientific participation.
Astrocytes are ubiquitous cells throughout brain tissue that play an essential role in neuronal survival. Yet, the mechanobiology of astrocytes, and in particular how their neuro-supportive role is affected by the mechanical stimuli that are generated during traumatic brain injury is not well understood. This research program will explore the mechanobiology of astrocytes, and investigate the hypothesis that the neuro-degenerative extracellular matrix environment produced by astrocytes following traumatic brain injury is triggered by mechanical stimuli. To explore this hypothesis, the research team will employ a custom impact bioreactor and cell culture system to (1) precisely apply traumatic brain injury mimetic impacts to populations of astrocytes in culture and (2) concentrate and collect the soluble (growth factors and cytokines) and insoluble (extracellular matrix) molecules released in response to impact loading. An improved understanding of the relationship between impact stimuli and the production of soluble and insoluble molecules will help elucidate the role astrocytes play in the neuro-degeneration processes that follow traumatic brain injury.