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

超声辅助基因转移至脑损伤后直接皮质神经发生

• 批准号: 8722168
• 负责人: Philip J Horner
• 金额: $ 40.49万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8722168
• 关键词: Adult; Adverse effects; Animal Model; Behavioral; Biological Assay; Bioluminescence; Blood Pressure; Brain; Brain Edema; Brain Injuries; Cause of Death; Cell Proliferation; Cells; Charge; Child; Clinical Trials; Cognitive; Development; Drug Formulations; Elderly; Emotional; Enzyme-Linked Immunosorbent Assay; Ependymal Cell; Evaluation; Fibroblast Growth Factor; Fibroblast Growth Factor 2; Focused Ultrasound Therapy; Frequencies; Gene Delivery; Gene Transfer; Genes; Goals; Healed; Hemolysis; Histology; Image; Immunofluorescence Immunologic; Immunohistochemistry; Injury; Intervention; Intracranial Pressure; Intraventricular Injections; Kinetics; Label; Lead; Lesion; Lipids; Magnetic Resonance Imaging; Mammals; Mediating; Medical; Membrane; Methods; Microbubbles; Modeling; Monitor; Motor; Neuroglia; Neuronal Differentiation; Neurons; Nucleic Acids; Outcome; Pathway interactions; Patients; Peptides; Polymers; Production; Proteins; Rattus; Recovery; Reporter Genes; Risk; Rodent Model; Site; Specificity; Stem cells; Stream; Structure of choroid plexus; Surface; System; Technology; Testing; Therapeutic; Transfection; Traumatic Brain Injury; Ultrasonography; United States; Work; cell type; cognitive recovery; disability; falls; functional improvement; healing; high risk; improved; improved functioning; in vitro Model; in vitro testing; in vivo; innovation; light scattering; migration; motor vehicle injury; nerve stem cell; neurogenesis; polymerization; public health relevance; relating to nervous system; repaired; response; stem; subventricular zone; therapeutic gene; transcription factor; transgene expression; vector; young adult

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. .

描述：脑损伤（TBI）通常是由汽车伤害引起的，年轻人和老年人跌落，每年都会遭受近170万人的伤害。 n除了是儿童和年轻人的主要死亡原因，TBI还是美国永久残疾的主要原因。目前尚无针对TBI治疗的治疗方法，主要的作用过程是最大程度地减少次要损害，这是由于血压，脑肿胀或颅内压的变化而导致的，而颅内压或颅内压的变化是由Initia损伤触发的。该项目的总体目标是首先开发一种耐受良好的转移手段 大脑中神经祖细胞的基因，然后使用该技术在受伤后指导皮质神经发生。我们建议使用聚焦的超声来增强由靶向聚合物递送载体介导的脑介导的脑中神经祖细胞的非病毒基因转移，从而使编码成纤维细胞生长因子-2和Neurogenin2的基因的递送，所显示的蛋白质，可增强神经发生和直接神经元分化。我们将在TBI的动物模型中评估诱导的迁移和神经元整合是否可以通过组织学，认知评估和运动评估的结合来改善功能。 。