DESCRIPTION: Traumatic brain injury (TBI), commonly caused by motor vehicle injury and falls in the young and elderly, afflicts nearly 1.7 million people in the United States each year. n addition to being a leading cause of death in children and young adults, TBI is also a major cause of permanent disability in the United States. There are currently no curative treatments for TBI, and the main course of action is to minimize secondary damage that results from changes in blood pressure, brain swelling, or intracranial pressure that is triggered by the initia injury. The overall goal of this project is to first develop a well-tolerated means of transferring genes to neural progenitor cells in the brain and then to use this technology to direct cortical neurogenesis after injury. We propose to use focused ultrasound to enhance non-viral gene transfer to neural progenitor cells in the brain mediated by a targeted polymer delivery vector, thus enabling the delivery of genes encoding fibroblast growth factor-2 and neurogenin2, proteins shown to enhance neurogenesis and direct neuron differentiation, respectively. We will evaluate in an animal model of TBI whether induced migration and increased neuronal integration can lead to functional improvement through a combination of histology, cognitive evaluations, and motor assessments. .