微管稳定剂缓释体增强脊髓固有束接力促进脊髓损伤的功能恢复

项目名称： 微管稳定剂缓释体增强脊髓固有束接力促进脊髓损伤的功能恢复

项目编号： No.81471271

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吴永超

作者单位： 华中科技大学

项目金额： 70万元

中文摘要： 脊髓损伤后的直接的神经信号传递途径被阻断，但是脊髓上神经束可以发出侧枝，和附近的脊髓固有神经元形成新突触连接，通过脊髓固有束接力传递神经信号，这被称为脊髓固有束接力的新理论。脊髓固有神经元数量更多，固有束轴突再生能力更强，是良好的干预靶点。本课题拟通过增强脊髓固有束接力来促进脊髓损伤后的功能恢复。近来发现临床常用的抗肿瘤药物微管稳定剂紫杉醇具有促进脊髓损伤后功能恢复的作用，紫杉醇通过不同于传统的促进轴突再生的新途径- - 稳定微管促进轴突再生，还能抑制胶质瘢痕。紫杉醇促进轴突再生的有效浓度范围较窄，需要稳定持续长期释放，药物缓释材料能起到这个作用。我们选用自行研制的RADA-FGL 多肽凝胶为缓释材料，同时RADA-FGL 多肽凝胶本身也具有促轴突再生和减少胶质瘢痕或空洞的作用。紫杉醇和RADA-FGL 多肽凝胶组成缓释体，并且有协同作用，共同促进脊髓固有束接力。

中文关键词： 脊髓损伤；紫杉醇；微管稳定；脊髓固有束；多肽

英文摘要： The direct signal conduction of axons is interrupted post spinal cord injury (SCI). Interestingly supraspinal tract can sprout and connect with propriospinal neurons nearby then new synapses and improved function of spinal cord can be observed. This phenomenon is called propriospinal relay. We propose here the enhanced propriospinal relay can increase the recovery of spinal cord injury.The Taxol is found to improve the functional recovery after spinal cord injury. Taxol is a antineoplastic drug and can stabilize microtubules. Microtubule stabilization can maintain the structure of axons and form regenerative growth cones so as to start axonal regeneration. Meanwhile the microtubules stabilization can suppress the glia scar formation. Microtubules stabilization is a new route to promote the axonal regeneration. Taxol has a narrow window of drug concentration for axonal regeneration, and a controlled release system is used to deliver taxol. This controlled release system includes functionalized RADA-FGL self-assembling peptide nanofiber hydrogel. RADA-FGL also serves as a scaffold to induce the axonal extension. Under these manipulations, more axons will be reserved, and the sprouting of axons will increase, and there will be more newly formed synapses between the supraspinal tract and propriospinal neurons, and more propriospinal tract-motor nurons connection. Eventually the input from the brain will be transferred downward through a rewiring pathway- propriospinal relay.

英文关键词： spinal cord injury;taxol;microtubule stabilization;propriospinal tract;peptide