Traumatic brain injury (TBI) is a leading cause of death, accounting for ~30% of all injury deaths in America, with over 2 million Americans acquiring some form of TBI. Approximately 20% of current service members have experienced some form of TBI. Many recent injuries have come in the form of exposures to blast from improvised explosive devices. Blast TBI triggers an activation of the immune system, generation of auto- antibodies, as well as infiltration of circulating immune cells into the central nervous system (CNS). These mechanisms occur in the brain as well as the retina. However, the individual role of cellular and humoral immunity causing neuron loss has not been thoroughly dissected. This proposal will define the role of auto- antibodies and circulating immune cells on the progression of blast-mediated visual loss in order to identify mechanisms that are amenable to therapy. The overall goal of this study is to determine which components of the immune response are necessary and sufficient to cause neuronal dysfunction and loss after blast-mediated TBI. Our central hypothesis is that blast-mediated traumatic brain injury activates cellular and humoral immune responses that lead to increased chronic neurodegeneration after TBI. Understanding how immune cells, autoantibodies, and complement protein affect eyes exposed to blast represents a critical knowledge gap. Our study should reveal novel therapeutic approaches utilizing drugs already approved for clinical use that can be immediately translated to benefit Veteran?s health.
Blast-mediated traumatic brain injury (TBI) is a leading cause of injury for Veterans. Blast TBI triggers an activation of the immune system, generation of auto-antibodies, as well as CNS infiltration of circulating immune cells. Our central hypothesis is that blast-mediated traumatic brain injury activates cellular and humoral immune responses that lead to increased chronic neurodegeneration after TBI. The overall goal of this study is to determine which components of this response are necessary and sufficient to cause neuronal loss and dysfunction after blast-mediated TBI. We will also determine if these responses can be modulated with currently approved medications.
