Department of Physiology and Cell Biology, The Ohio State University Medical Center, Columbus, 43210, USA.
Brain Res Bull. 2011 Mar 10;84(4-5):317-26. doi: 10.1016/j.brainresbull.2010.06.002. Epub 2010 Jun 15.
Exercise provides a number of important benefits after spinal cord injury in clinical studies and animal models. However, the amount of functional improvement in overground locomotion obtained with exercise alone has been limited thus far, for reasons that are still poorly understood. One hypothesis is that the complex network of endogenous extracellular matrix components, including chondroitin sulfate proteoglycans (CSPGs), can inhibit exercise-induced remodeling and limit plasticity of spared circuitry in the adult central nervous system. Recent animal studies have shown that chondroitinase ABC (ChABC) can enhance plasticity in the adult nervous system by cleaving glycosaminoglycan sidechains from CSPGs. In this article we review the current literature on plasticity observed with locomotor training and following degradation of CSPGs with ChABC and then present a rationale for the use of exercise combined with ChABC to promote functional recovery after spinal cord injury. We also present results of a preliminary study that tested the simplest approach for combining these treatments; use of a single intraparenchymal injection of ChABC administered to the lumbar enlargement of mice with voluntary wheel running exercise after a mid-thoracic spinal contusion injury. The results are negative, yet serve to highlight limitations in our understanding of the most effective protocols for combining these approaches. Further work is directed to identify the timing, type, and quantity of exercise and pharmacological interventions that can be used to maximize functional improvements by strengthening appropriate synaptic connections.
运动在临床研究和动物模型中为脊髓损伤后提供了许多重要的益处。然而，迄今为止，运动单独在改善地面运动功能方面的效果有限，其原因仍不甚清楚。一种假设是，包括硫酸软骨素蛋白聚糖 (CSPG) 在内的内源性细胞外基质成分的复杂网络可以抑制运动诱导的重塑，并限制成年中枢神经系统中保留电路的可塑性。最近的动物研究表明，软骨素酶 ABC（ChABC）可以通过从 CSPG 上裂解糖胺聚糖侧链来增强成年神经系统的可塑性。在本文中，我们回顾了关于运动训练引起的可塑性以及 ChABC 降解 CSPG 后观察到的可塑性的现有文献，然后提出了一个使用运动联合 ChABC 促进脊髓损伤后功能恢复的基本原理。我们还介绍了一项初步研究的结果，该研究测试了将这些治疗方法结合起来的最简单方法；在中胸段脊髓挫伤损伤后，使用 ChABC 对小鼠进行腰椎扩大的单次脑室内注射，并结合自愿轮跑运动。结果是否定的，但足以凸显出我们对这些方法的最有效组合方案的理解存在局限性。进一步的工作旨在确定运动和药物干预的时间、类型和数量，这些干预可以通过加强适当的突触连接来最大限度地提高功能改善。
