Ultrasound-aided gene transfer to direct cortical neurogenesis after brain injury

产品说明：创伤性脑损伤（TBI），通常由机动车损伤和年轻人和老年人的福尔斯跌倒引起，每年折磨着美国近170万人。除了是儿童和年轻人死亡的主要原因外，TBI也是美国永久性残疾的主要原因。目前还没有针对TBI的治愈性治疗，并且主要的行动过程是最小化由初始损伤触发的血压、脑肿胀或颅内压变化引起的继发性损伤。该项目的总体目标是首先开发一种耐受性良好的转移手段， 基因到大脑中的神经祖细胞，然后使用这种技术来指导受伤后的皮层神经发生。我们建议使用聚焦超声，以提高非病毒基因转移到神经祖细胞在大脑中介导的有针对性的聚合物传递载体，从而使编码成纤维细胞生长因子-2和neurogenin 2，蛋白质，以增强神经发生和直接神经元分化，分别交付的基因。我们将通过组织学、认知评估和运动评估的组合，在TBI动物模型中评估诱导的迁移和增加的神经元整合是否可以导致功能改善。.

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. .