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) 会导致严重残疾，但几乎在所有情况下，损伤后第一年功能都会有所恢复。我们打算更多地了解这些自发恢复过程，以便尝试开发疗法来提高恢复程度。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，以了解传导何时受到损害以及随时间的推移如何变化。我们有一种酶疗法可以溶解 SCI 疤痕组织中存在的分子。我们需要优化向脊髓输送大量这种酶的方法，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传递这种酶，使其进入最需要它的脊髓疤痕处的细胞，我们将测试这是否可以改善功能。我们还将使用新技术来显示这种疗法后萌芽的新纤维是否可以通过使用仅当细胞之间存在活动时才会发光的特殊荧光探针来研究神经细胞连接性来将信号传输到其他神经细胞。最后，我们将使用技术来显示用这种疗法治疗时受损细胞中发生的分子信号变化，以便我们可以用新药物直接靶向它们。这项研究对于制定治疗脊柱损伤患者的治疗策略非常重要。