The following Phd student project will examine the interaction between brain vascular mural cells and tau and their contribution to traumatic brain injury (TBI) pathophysiology. Mural cell loss in the brain vasculature is a common feature of many neurodegenerative disorders, and the loss of these cells may explain the accumulation of solutes found in these disease states. In our prior studies, we observed a progressive reduction in cerebrovascular mural cell density following repetitive mild TBI (r-mTBI) in our mouse model, and found that isolated brain vessels from r-mTBI animals were less able to internalize tau than non-injured animals. Importantly, the mural cell perturbations observed in our mouse r-mTBI model coincided with an accumulation of total tau, phosphorylated tau, and oligomeric tau species in the brain. The goals of the new PhD student project are to, 1) evaluate the impact of mural cells on tau pathology following TBI in mouse and human brain specimens, 2) determine the role of mural cells in tau elimination following TBI and, 3) examine the influence of mural cells on tau movement in the brain. 

This project will utilize a variety of biochemical and molecular biology techniques including: immunoblotting, ELISA, cell culture, isolation of brain vasculature, immunohistochemistry, and particularly, confocal microscopy. Moreover, an important aspect of this project will involve the manipulation of animals including: delivery of traumatic brain injuries, intracranial administration of molecules, and blood and tissue collection.