Neuroregulatory factors in traumatic brain injury

Abstract

The mechanisms underlying neuron loss in central nervous system disorders are incompletely understood. We have previously identified dysregulation in several pathways important to neuronal health. In this study, we focus on identifying regulatory factors that could be used to protect and preserve neuronal function following traumatic brain injury (TBI). Elucidation of factors involved in neuronal death will provide targets to achieve therapeutic benefits during a narrow window of opportunity after TBI. Using an in vitro cell injury model, we identified several transcription factors that are upregulated that can result in a proapoptotic gene expression profile, including E26 avian leukemia oncogene 1 (ETS1), interferon regulatory factors (IRF3 and 6), MAD homolog 3 (Smad3), and Wilms tumor homolog (WT1). The expression levels of these factors were elevated about 1.7 fold and 3.5 fold in the case of ETS1. Our data indicate that inflammatory responsive transcription factors, implicated in apoptosis in other tissues, are also important in cell loss in the brain. The identification of these and other factors that regulate neuronal survival following TBI may represent an attractive target for pharmacological intervention. This study was supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, the Bay Pines Foundation, and the Alzheimer's Association.