King's College London, Neurorestoration Group, Wolfson Centre for Age-Related Diseases, Guy's Campus, London, United Kingdom.
Brain Res Bull. 2011 Mar 10;84(4-5):306-16. doi: 10.1016/j.brainresbull.2010.06.015. Epub 2010 Jul 8.
Chondroitin sulphate proteoglycans (CSPGs) are potent inhibitors of growth in the adult CNS. Use of the enzyme chondroitinase ABC (ChABC) as a strategy to reduce CSPG inhibition in experimental models of spinal cord injury has led to observations of a remarkable capacity for repair. Here we review the evidence that treatment with ChABC, either as an individual therapy or in combination with other strategies, can have multiple beneficial effects on promoting repair following spinal cord injury. These include promoting regeneration of injured axons, plasticity of uninjured pathways and neuroprotection of injured projection neurons. More importantly, ChABC therapy has been demonstrated to promote significant recovery of function to spinal injured animals. Thus, there is robust pre-clinical evidence demonstrating beneficial effects of ChABC treatment following spinal cord injury. Furthermore, these effects have been replicated in a number of different injury models, with independent confirmation by different laboratories, providing an important validation of ChABC as a promising therapeutic strategy. We discuss putative mechanisms underlying ChABC-mediated repair as well as potential issues and considerations in translating ChABC treatment into a clinical therapy for spinal cord injury.
硫酸软骨素蛋白聚糖（CSPGs）是成人中枢神经系统生长的有效抑制剂。在脊髓损伤的实验模型中，使用酶软骨素酶 ABC（ChABC）作为降低 CSPG 抑制的策略，导致了对修复能力的显著观察。在这里，我们回顾了证据，表明 ChABC 治疗无论是作为单一疗法还是与其他策略联合使用，都可以对脊髓损伤后的修复产生多种有益影响。这些包括促进损伤轴突的再生、未损伤途径的可塑性和损伤投射神经元的神经保护。更重要的是，ChABC 治疗已被证明可促进脊髓损伤动物功能的显著恢复。因此，有大量的临床前证据表明脊髓损伤后 ChABC 治疗具有有益的作用。此外，这些效果已经在许多不同的损伤模型中得到复制，并得到了不同实验室的独立证实，为 ChABC 作为一种有前途的治疗策略提供了重要的验证。我们讨论了 ChABC 介导的修复的潜在机制，以及将 ChABC 治疗转化为脊髓损伤的临床治疗的潜在问题和考虑因素。
