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

脊髓损伤（SCI）导致严重的残疾，但在几乎所有的情况下，在损伤后的第一年，功能都有一定的恢复。我们打算更多地了解这些自发恢复过程，以便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，我们将研究脊髓损伤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随时间的变化情况。我们有一种酶疗法可以溶解存在于脊髓损伤瘢痕组织中的分子。我们需要优化输送大量这种酶到脊髓的方法，同时尽量减少重复给药的创伤。我们有一种运送酶的新方法，这样它就能进入最需要酶的脊髓疤痕处的细胞，我们将测试这是否能改善功能。我们还将使用新颖的技术，通过使用特殊的荧光探针研究神经细胞之间的连接，来显示在这种治疗后发芽的新纤维是否可以向其他神经细胞传递信号，这种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受伤细胞在接受这种治疗时发生的分子信号变化，这样我们就可以直接用新药靶向它们。该研究对制定治疗脊髓损伤患者的治疗策略具有重要意义。

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.