Repair of the corticospinal tract

皮质脊髓束的修复

• 批准号: MR/R004463/1
• 负责人: James Fawcett
• 金额: $ 81.4万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR004463%2F1
• 关键词: Repair; corticospinal; tract

After spinal cord injury patients lose sensation and are paralysed because the nerve fibres connecting the brain with the body are cut in the spinal cord. To restore full function these damaged fibres must be made to regenerate. Effective regeneration in the spinal cord has not been possible, but recent advances in Cambridge have made it possible to restore sensory regeneration in the spinal cord. Regeneration of motor fibres is more difficult, because unlike sensory fibres, the motor fibres mature to exclude many of the molecules needed for regeneration. The plan for this application is to bring together the method that made sensory regeneration possible with four candidate methods to enable growth-related molecules to be transported into the motor nerve fibres. The molecules that enable nerve fibre growth are integrins, which are transported into sensory fibres but not motor fibres. Research on transport mechanisms has developed four methods the enable integrins to be transported into mature nerve fibres and to restore their ability to regenerate in a tissue culture model.The plan for the application is to develop viral vectors suitable for use in rats for each of these treatments. The treatments will then be tested in combination to find out the most powerful treatment for inducing regeneration. Some of the successful combinations will then be tested in quick proof of principle experiments in rats with partial spinal cord damage to identify the best method for restoring regeneration. Finally the best two treatments will be tested in a full experiment in which regeneration and behavioural recovery will be measured.

脊髓损伤后，患者失去知觉并瘫痪，因为连接大脑和身体的神经纤维在脊髓中被切断。为了恢复全部功能，这些受损的纤维必须再生。脊髓的有效再生一直是不可能的，但剑桥最近的进展使脊髓感觉再生的恢复成为可能。运动纤维的再生更加困难，因为与感觉纤维不同，运动纤维成熟后会排斥许多再生所需的分子。这项应用的计划是将使感觉再生成为可能的方法与四种候选方法结合起来，使生长相关分子能够被运送到运动神经纤维中。使神经纤维生长的分子是整合素，它被输送到感觉纤维而不是运动纤维。对转运机制的研究已经开发出四种方法，使整合素能够被转运到成熟的神经纤维中，并在组织培养模型中恢复其再生能力。该应用的计划是开发适用于大鼠的病毒载体，用于每种治疗。然后将对这些处理进行组合测试，以找出诱导再生的最有效处理。然后，一些成功的组合将在部分脊髓损伤的大鼠中进行快速原理实验，以确定恢复再生的最佳方法。最后，最好的两种治疗方法将在一个完整的实验中进行测试，其中再生和行为恢复将被测量。

项目成果

Quantifying inter-organelle membrane contact sites using proximity ligation assay in fixed optic nerve sections.

使用固定视神经截面中的接近连接测定法量化轨道间膜接触位点。

• DOI: 10.1016/j.exer.2021.108793
• 发表时间: 2021-12
• 期刊: Experimental eye research
• 影响因子: 3.4
• 作者: Ching J;Osborne A;Eva R;Prudent J;Yu-Wai-Man P
• 通讯作者: Yu-Wai-Man P

Regenerative capacity of neural tissue scales with changes in tissue mechanics post injury

神经组织的再生能力随损伤后组织力学的变化而变化

• DOI: 10.1101/2022.12.12.517822
• 发表时间: 2022
• 作者: Carnicer-Lombarte A

PI 3-kinase delta enhances axonal PIP3 to support axon regeneration in the adult CNS

PI 3-激酶 delta 增强轴突 PIP3 以支持成人中枢神经系统的轴突再生

• DOI: 10.1101/787994
• 发表时间: 2019
• 作者: Barber A

Integrin-Driven Axon Regeneration in the Spinal Cord Activates a Distinctive CNS Regeneration Program.

• DOI: 10.1523/jneurosci.2076-22.2023
• 发表时间: 2023-06-28
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Cheah, Menghon;Cheng, Yuyan;Petrova, Veselina;Cimpean, Anda;Jendelova, Pavla;Swarup, Vivek;Woolf, Clifford J.;Geschwind, Daniel H.;Fawcett, James W.
• 通讯作者: Fawcett, James W.