Transcription Factors and Traumatic Brain Injury

Traumatic Brain Injury (TBI) affects 1.4 million people annually in the U.S., resulting in substantial neuronal loss for which there is currently no effective treatment. Even mild injuries have long‐term consequences that interfere with the life of the patient and impose a burden on our healthcare system. Unfortunately, TBI is the signature affliction of recent combat operations with an incidence of approximately 15%. The molecular processes that regulate neuronal death following TBI are incompletely understood. In effort to elucidate these mechanisms and to identify novel therapeutic targets, we are investigating transcription factor signaling. We, and others, have observed transcription factor dysregulation in several disease states, including TBI, disrupting the balance of harmful and protective gene expression resulting in neuronal death. Transcription factors, such as nuclear factor erythroid‐derived‐like 2 (Nrf2), may provide therapeutic targets as slight adjustments alter downstream genes and improve neuronal survival. Our experiments using human TBI samples, a mouse closed head injury model, and biaxial stretch injury of cultured neurons, suggest that an increase in Nrf2 by treatment with activator tert‐Butylhydroquinone (tBHQ) is neuroprotective. Research supported by the Dept. of Veterans Affairs (Veterans Health Administration, Office of R&D, Biomedical Laboratory R&D) and the Bay Pines Foundation.