Benowitz Larry I, Yin Yuqin
Laboratories for Neuroscience Research in Neurosurgery and Neurobiology Program, Children's Hospital, Boston, Massachusetts, USA.
Dev Neurobiol. 2007 Aug;67(9):1148-65. doi: 10.1002/dneu.20515.
In general, neurons in the mature mammalian central nervous system (CNS) are unable to regenerate injured axons, and neurons that remain uninjured are unable to form novel connections that might compensate for ones that have been lost. As a result of this, victims of CNS injury, stroke, or certain neurodegenerative diseases are unable to fully recover sensory, motor, cognitive, or autonomic functions. Regenerative failure is related to a host of inhibitory signals associated with the extracellular environment and with the generally low intrinsic potential of mature CNS neurons to regenerate. Most research to date has focused on extrinsic factors, particularly the identification of inhibitory proteins associated with myelin, the perineuronal net, glial cells, and the scar that forms at an injury site. However, attempts to overcome these inhibitors have resulted in relatively limited amounts of CNS regeneration. Using the optic nerve as a model system, we show that with appropriate stimulation, mature neurons can revert to an active growth state and that when this occurs, the effects of overcoming inhibitory signals are enhanced dramatically. Similar conclusions are emerging from studies in other systems, pointing to a need to consider combinatorial treatments in the clinical setting.
一般来说，成熟哺乳动物中枢神经系统（CNS）中的神经元无法再生受损轴突，未受损的神经元也无法形成新的连接来补偿已丧失的连接。因此，中枢神经系统损伤、中风或某些神经退行性疾病的患者无法完全恢复感觉、运动、认知或自主功能。再生失败与一系列与细胞外环境相关的抑制信号以及成熟中枢神经系统神经元普遍较低的内在再生潜力有关。迄今为止，大多数研究都集中在外在因素上，特别是与髓磷脂、神经元周围网、神经胶质细胞以及损伤部位形成的瘢痕相关的抑制蛋白的鉴定。然而，克服这些抑制剂的尝试仅带来了相对有限的中枢神经系统再生。以视神经作为模型系统，我们发现，通过适当的刺激，成熟神经元可以恢复到活跃的生长状态，而当这种情况发生时，克服抑制信号的效果会显著增强。其他系统的研究也得出了类似的结论，这表明在临床环境中需要考虑联合治疗。
