Specific Aim 3.5: The overall aim of this project is to develop novel antioxidant therapies for traumatic brain injury (TBI) using modified nanotubes that are capable of addressing, for the first time, key components of the "neurovascular unit." This nanotube technology may allow the flexibility to target specific central nervous system compartments such as the intravascular space, endothelial cells, and possibly the brain parenchyma, by altering bound molecules that determine this distribution. Such an achievement will not only allow the testing of important hypotheses, such as the contribution of vascular dysfunction to brain injury, but the possibility of a targeted treatment that ultimately will reduce the likelihood of toxicity while increasing the chances of benefit.

Specific Aim 2.2: In this study we propose to use magnetoencephalography (MEG) to detect and characterize focal abnormalities in neurophysiological function in patients with mild TBI (MTBI) and post-traumatic stress disorder (PTSD) for the purpose of distinguishing between the two. MEG is a completely noninvasive imaging modality that is able to provide information regarding focal abnormalities in the brain. MEG has been shown to be sensitive to cognitive complaints in patients with MTBI and to be more sensitive to these deficits than electroencephalography. In addition, neurophysiological abnormalities differentiate patients with MTBI and PTSD in some studies. We also propose to explore the relationship between diffusion tensor imaging (DTI) and MEG findings. While MEG provides data regarding focal abnormalities in neural response in the cortex, DTI reveals the status of white matter tracts that form the intracortical connections. Thus, MEG, in combination with DTI, may lead to identification of more distinct, replicable patterns of brain abnormalities in subjects with PTSD and MTBI that may lead to better differentiation between these groups of patients, as well as from patients with a combination of both disorders.