The events that take place at the molecular level in traumatic brain injury (TBI) are not well characterized. We do know that immediately following a TBI, profound inflammatory responses are initiated, and several genes and proteins involved in inflammatory processes are aberrantly expressed. The mechanism we propose to study, DNA methylation, is intrinsically linked to the regulation of gene expression. Thus, the purpose of our investigation is to elucidate how patterns of DNA methylation may vary by TBI diagnosis and by severity of the disease. TBI cases with existing serum samples housed at the Department of Defense Serum Repository will be identified using diagnostic codes for TBI. We will identify an appropriate control group for which there was never a diagnosis of TBI. For each TBI case and each control, a serum sample drawn prior to first Operation Iraqi Freedom/Operation Enduring Freedom deployment and a sample drawn after that deployment will be identified. DNA will be extracted from each serum sample, and DNA methylation quantified globally and in the following inflammatory genes, IL-1beta, IL-6, IL-8, IL-10, and cyclin A1 and D3. Comparisons will be made for patterns of DNA methylation between cases (stratified into mild, moderate, and severe) and controls and between pre- and post-deployments for both cases and controls. This study will help to elucidate the molecular sequelae of brain injury and will fuel novel therapeutic approaches to TBI therapy, particularly since modifications in DNA methylation can potentially be reversed.
|Effective start/end date||1/01/07 → 31/12/07|
- U.S. Department of Defense: $217,104.00