Promoting axon regneration and functional recovery after spinal cord injury

促进脊髓损伤后轴突再生和功能恢复

• 批准号: 7809817
• 负责人: ZHIGANG HE
• 金额: $ 44.12万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7809817
• 关键词: Adult; Axon; Brain; Brain region; Corticospinal Tracts; Development; Dorsal; Down-Regulation; Environment; Failure; Fiber; Genetic; Injury; Lateral; Lesion; Motor; Motor Pathways; Movement; Mus; Mutant Strains Mice; Natural regeneration; Neurons; Optic Nerve Injuries; PTEN gene; Pathway interactions; Protein Biosynthesis; Recovery of Function; Retinal Ganglion Cells; Sensory; Sirolimus; Site; Spinal Cord; Spinal cord injury; Therapeutic; Tuberous Sclerosis; axon regeneration; axonal sprouting; extracellular; in vivo; inhibitor/antagonist; injured; insight; juvenile animal; mTOR protein; mature animal; research study; restoration

Spinal cord injury disrupts the connections between the brain and spinal cord, often resulting in the loss of sensory and motor function below the lesion site. The most important reason for such permanent functional deficits is the failure of injured axons to regenerate after injury. In principle, the functional recovery could be achieved by two forms of axonal regrowth: the regeneration of lesioned axons which will reconnect with their original targets and the sprouting of spared axons that form new circuits and compensate for the lost function. Our recent studies reveal the activity of the mammalian target of rapamycin (mTOR) pathway, a major regulator of new protein synthesis, as a critical determinant of axon regrowth in the adult retinal ganglion neurons. This proposed study will focus on examining the possibility of whether manipulating the mTOR activity could promote the regrowth of descending corticospinal axons and restoration of lost functions after spinal cord injury. We expect that these experiments will provide important insights into the therapeutic potential of manipulating mTOR pathway in promoting axon regrowth and functional recovery after spinal cord injury.

脊髓损伤破坏了大脑和脊髓之间的连接，通常 导致损伤部位以下的感觉和运动功能丧失。最 这种永久性功能缺陷的一个重要原因是受损的轴突不能 损伤后再生。原则上，功能恢复可以通过两种方法来实现 轴突再生的形式：受损轴突的再生， 它们最初的目标和形成新回路的备用轴突的发芽， 弥补失去的功能。我们最近的研究揭示了哺乳动物 雷帕霉素（mTOR）途径的靶点是新蛋白质合成的主要调节因子，作为一种 成年视网膜神经节神经元轴突再生的关键决定因素。这一拟议 这项研究将集中在检查是否操纵mTOR活性的可能性， 能促进皮质脊髓下行轴突的再生和丢失的神经元的恢复。 脊髓损伤后的功能。我们希望这些实验将提供重要的 操纵mTOR通路促进轴突生长的治疗潜力 脊髓损伤后的再生和功能恢复。