Acute and chronic spinal cord injury: novel studies of synaptogenesis, plasticity and mechanisms of repair

急性和慢性脊髓损伤：突触发生、可塑性和修复机制的新研究

• 批准号: G1002055/1
• 负责人: Elizabeth Bradbury
• 金额: $ 243.85万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1002055%2F1
• 关键词: Acute; chronic; spinal; cord; injury

Spinal cord injury (SCI) leads to severe disability, but in nearly all cases there is some recovery in function over the first year following injury. We intend to find out more about these spontaneous recovery processes in order to try and develop therapies to increase the extent of recovery. For example, using special recording techniques we will study changes in nerve fibre conduction at early and late stages following SCI to see when conduction is compromised and how this changes over time. We have an enzyme therapy which can dissolve molecules that are present in SCI scar tissue. We need to optimise ways of delivering large amounts of this enzyme to the spinal cord while minimising the trauma of repeated administration. We have a new way of delivering the enzyme so that it gets into cells at the spinal cord scar, where it is most needed, and we will test whether this can improve function. We will also use novel techniques to show whether new fibres that have sprouted following this therapy can transmit signals to other nerve cells by studying nerve cell connectivity using special fluorescent probes that light up only when there is activity between cells. Finally we will use techniques to show the molecular signals that change in injured cells when treated with this therapy so that we can target them directly with new drugs. This research will be important for developing therapeutic strategies for treating spinal injured patients.

脊髓损伤（SCI）会导致严重的残疾，但在几乎所有的情况下，在受伤后的第一年内都会有一些功能恢复。我们打算更多地了解这些自发恢复过程，以尝试和开发治疗方法来增加恢复的程度。例如，使用特殊的记录技术，我们将研究SCI后早期和晚期神经纤维传导的变化，以了解传导何时受损以及如何随时间变化。我们有一种酶疗法可以溶解SCI疤痕组织中的分子。我们需要优化将大量这种酶输送到脊髓的方法，同时最大限度地减少重复给药的创伤。我们有一种新的方法来输送这种酶，使它进入脊髓疤痕处的细胞，那里是最需要的，我们将测试这是否可以改善功能。我们还将使用新的技术来显示在这种疗法后发芽的新纤维是否可以通过使用特殊的荧光探针研究神经细胞的连接性来将信号传输到其他神经细胞，这些荧光探针只有在细胞之间有活动时才会发光。最后，我们将使用技术来显示在用这种疗法治疗时受损细胞中发生变化的分子信号，以便我们可以用新药直接靶向它们。这项研究将是重要的发展战略，治疗脊髓损伤的病人。