Promoting axon regneration and functional recovery after spinal cord injury

脊髓损伤会破坏大脑和脊髓之间的连接，通常 导致病变部位以下的感觉和运动功能丧失。最多的 这种永久性功能缺陷的重要原因是损伤的轴突未能 受伤后会再生。原则上，功能恢复可通过两种方式实现 轴突再生的形式：受损轴突的再生将与 它们最初的目标和形成新回路的备用轴突的萌发 补偿失去的功能。我们最近的研究揭示了哺乳动物的活动 雷帕霉素(MTOR)途径的靶点，作为一种新的蛋白质合成的主要调节因子 成年视网膜神经节神经元轴突再生的关键决定因素。这项建议 研究将集中于检查是否可能操纵mTOR活动 能促进皮质脊髓下行轴突的再生和修复 脊髓损伤后的功能。我们预计这些实验将提供重要的 操纵mTOR通路促进轴突的治疗潜力 脊髓损伤后的再生和功能恢复。

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.