Sosa I, Reyes O, Kuffler D P
Section of Neurosurgery, Medical Sciences Campus, UPR, 201 Boulevard del Valle, San Juan 00901, Puerto Rico.
Exp Neurol. 2005 Sep;195(1):7-15. doi: 10.1016/j.expneurol.2005.04.016.
No clinical techniques induce restoration of neurological losses following spinal cord trauma. Peripheral nerve damage also leads to permanent neurological deficits, but neurological recovery can be relatively good, especially if the ends of a transected nerve are anastomosed soon after the injury. The time until recovery generally depends on the distance the axons must regenerate to their targets. Neurological recovery following the destruction of a length of a peripheral nerve requires a graft to bridge the gap that is permissive to, and promotes, axon regeneration. But neurological recovery is slow and limited, especially for gaps longer than 1.5 cm, even using autologous peripheral nerve grafts. Without a reliable means of bridging long nerve gaps, such injuries commonly result in amputations. Promoting extensive neurological recovery requires techniques that simultaneously provide protection to injured neurons and increase the numbers of neurons that extend axons, while inducing more rapid and extensive axon regeneration across long nerve gaps. Although conduits filled with various materials enhance axon regeneration across short nerve gaps, pure sensory nerve graft remains the gold standard for use across long nerve gaps, even though they lead to only limited neurological recovery. Consistent results demonstrate that several immunosuppressive agents enhance the number of axons and the rate at which they regenerate. This review examines the roles played by immunosuppressants, especially FK506, with primary focus on its role as a neuroprotectant and neurotrophic agent, and its potential clinical use to promote improved neurological recovery following peripheral nerve and spinal cord injuries.
目前尚无临床技术能够促使脊髓损伤后神经功能缺失得以恢复。周围神经损伤同样会导致永久性神经功能缺损，不过神经功能恢复情况相对较好，尤其是在神经横断伤后若能尽快吻合神经断端。恢复所需时间通常取决于轴突再生至其靶标的距离。一段周围神经被破坏后的神经功能恢复需要移植神经来桥接间隙，该间隙要有利于并促进轴突再生。但神经功能恢复缓慢且有限，特别是对于长度超过1.5厘米的间隙，即便使用自体周围神经移植也是如此。若没有可靠的方法来桥接长神经间隙，此类损伤通常会导致截肢。促进广泛的神经功能恢复需要这样的技术，即既能同时为受损神经元提供保护，又能增加伸出轴突的神经元数量，同时诱导轴突在长神经间隙上更快速、广泛地再生。尽管填充各种材料的导管可增强轴突在短神经间隙上的再生，但纯感觉神经移植仍是跨越长神经间隙使用的金标准，即便其只能带来有限的神经功能恢复。一致的结果表明，几种免疫抑制剂可增加轴突数量及其再生速率。本综述探讨了免疫抑制剂，尤其是FK506所起的作用，主要聚焦于其作为神经保护剂和神经营养剂的作用，以及其在促进周围神经和脊髓损伤后神经功能恢复改善方面的潜在临床应用。
