Department of Physiology, Neuroscience and Development, University of Cambridge, Cambridge, United Kingdom.
Front Neural Circuits. 2017 Nov 6;11:84. doi: 10.3389/fncir.2017.00084. eCollection 2017.
Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the "new" locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury.
寻找治疗脊髓损伤 (SCI) 的方法侧重于通过促进损伤部位的再生来重新连接脊髓。然而，尽管再生对于恢复是必要的，但它本身可能还不够。这大概反映了再生输入需要与脊髓适当相互作用，使损伤下的网络特性成为恢复的另一个影响因素。本综述总结了我们在七鳃鳗中的工作，七鳃鳗是 SCI 研究的模型系统。我们比较了未损伤动物和接受完全脊髓损伤动物的运动行为（游泳）和下行输入、运动网络和感觉输入的特性。在大多数（约 90%）的动物中，损伤后的游泳参数恢复到与未损伤动物匹配的水平。来自单个再生轴突的突触输入也与未损伤动物的特性相匹配，尽管这与释放参数的变化有关。这表明在这些突触上没有任何补偿，因为即使再生总是不完全的，也会出现下行驱动的减少。代偿似乎是通过损伤部位以下和以上的运动网络和本体感受系统中的细胞和突触特性的多种变化来实现的。因此，运动表现的恢复不仅仅是脊髓两侧的重新连接，而是反映了脊髓的分布式和多样化变化。虽然运动网络的变化本身不足以恢复，但它们可以通过补偿下行驱动的减少来促进运动输出。增强的感觉反馈反过来可能是一种必要的适应，它可以监测和调整来自“新”运动网络的输出。SCI 后可能需要改变运动系统的不同组成部分及其相互作用，而不是单一的方面。如果这些是普遍特征，并且可以与哺乳动物系统进行比较，那么这些效应似乎是保守的，提高高等脊椎动物的功能恢复需要干预措施来产生有利于恢复的最佳脊髓条件。在哺乳动物脊髓中进行这些分析具有挑战性，但较低等的脊椎动物系统应该有助于确定最佳脊髓对损伤的反应原则。
