完全性脊髓损伤再生机制的探讨

Review of the regeneration mechanism of complete spinal cord injury

脊髓损伤修复迄今仍是世界性的医学难题。戴建武教授团队近20年来专注脊髓损伤再生修复研究,建立了哺乳动物脊髓大段缺损全横断损伤模型,包括啮齿类、犬及非人灵长类全横断脊髓损伤模型,并于2015年1月16日在国际上首先开展了神经再生胶原支架材料修复完全性脊髓损伤的临床研究。文章依据领域研究进展,分析了脊髓完全性损伤后运动功能恢复的3种可能机制:(1)运动神经长轴突再生通过损伤区域;(2)损伤区新生的神经元连接损伤的两个断端,形成连接;(3)前述两种机制都存在。大量不同动物全横断脊髓损伤模型及再生修复研究结果均表明,神经再生胶原支架移植治疗全横断脊髓损伤动物是通过引导内源神经元形成桥接改善运动功能。在不同脊髓损伤模型中,特别是大段缺损全横断脊髓损伤模型中,长的轴突生长非常有限,无法满足动物运动功能恢复的要求。在全横断脊髓损伤动物模型中,通过功能修饰的神经再生胶原支架移植促进新神经元产生并形成桥接改善运动功能相比引导运动轴突再生更可行,是全横断脊髓损伤后运动功能恢复的主要机制。但在再生修复时如何促进更多的神经元产生、形成正确的桥接并实现更好的运动功能恢复等都是亟待解决的重要问题。

Spinal cord injury（SCI）, especially the complete SCI, usually results in complete paralysis below the level of the injury and seriously affects the patient＇s quality of life. SCI repair is still a worldwide medical problem. In the last twenty years, Professor DAI Jianwu and his team pioneered complete SCI model by removing spinal tissue with varied lengths in rodents, canine, and non-human primates to verify therapeutic effect of different repair strategies.Moreover, they also started the first clinical study of functional collagen scaffold on patients with acute complete SCI on January 16 th, 2015. This review mainly focusses on the possible mechanisms responsible for complete SCI. In common,recovery of some sensory and motor functions post complete SCI include the following three contributing reasons.（1） Regeneration of long ascending and descending axons throughout the lesion site to re-connect the original targets;（2）New neural circuits formed in the lesion site by newly generated neurons post injury, which effectively re-connect the transected stumps;（3） The combined effect of（1） and（2）. The numerous studies have confirmed that neural circuits rebuilt across the injury site by newborn neurons might be the main mechanisms for functional recovery of animals from rodents to dogs. In many SCI model, especially the complete spinal cord transection model, many studies have convincingly demonstrated that the quantity and length of regenerated long descending axons, particularly like CST fibers, are too few to across the lesion site that is millimeters in length to realize motor functional recovery. Hence, it is more feasible in guiding neuronal relays formation by bio-scaffolds implantation than directing long motor axons regeneration in improving motor function of animals with complete spinal cord transection. However, some other issues such as promoting more neuronal relays formation, debugging wrong connections, and maintaining adequate neural circuits for functional recovery are urgent problems to be addressed.