Neutrophil Activation after Traumatic Brain Injury

PROJECT NARRATIVE Traumatic brain injury (TBI), a leading cause of mortality and long-term disability worldwide, debilitates or kills more individuals that breast cancer, AIDS, multiple sclerosis, and spinal cord injury combined. Preventative measures reduce injury incidence and/or severity, yet one-third of hospitalized TBI patients die from secondary pathological processes that develop during supervised medical care. Our conceptually innovative studies will demonstrate that toll-like receptor-4 induced formation of neutrophil extracellular traps (NETs) provides a scaffold for cerebral microthrombus formation, establishing a mechanistic framework for the development of novel therapeutic approaches to improve cerebral recirculation after TBI.