中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (5): 948-952.doi: 10.4103/1673-5374.324830

• 综述:周围神经损伤修复保护与再生 • 上一篇    下一篇

锂能否增强周围神经创伤后轴突再生和神经功能恢复的程度?

  

  • 出版日期:2022-05-15 发布日期:2021-11-08

Can lithium enhance the extent of axon regeneration and neurological recovery following peripheral nerve trauma?

Damien P. Kuffler*   

  1. Institute of Neurobiology, Medical Sciences Campus, University of Puerto Rico, San Juan, PR, USA
  • Online:2022-05-15 Published:2021-11-08
  • Contact: Damien P. Kuffler, PhD, dkuffler@hotmail.com.

摘要: Neural Regen Res:锂增加轴突再生和神经功能恢复的能力和可靠性
目前周围神经缺损外科修复“金标准”技术是通过自体神经移植,然而自体移植物仅在短距离神经缺损、年轻患者中以及在神经创伤后短时间内进行修复时才能得到较为满意的效果。即使在最好的条件下,仍有>50% 的患者达不到良好效果。尽管已经测试了许多替代技术,但没有一种技术比自体移植有效。满足这些标准的一种化合物是锂。前期研究表明在小鼠视神经和大鼠脊髓损伤之后,锂的注射增强了轴突再生和功能恢复。在大鼠模型中,锂给药可改善腹侧根部撕脱和再植后的功能性运动恢复。在大鼠中,将锂注入桥接坐骨神经间隙的导管中可显著增加雪旺细胞密度,并且距离轴突跨越间隙再生。在小鼠面部神经压伤后,锂给药刺激髓鞘基因的表达,恢复髓鞘结构,并加速胡须运动功能的恢复。
来自美国波多黎各大学的Damien P. Kuffler认为,轴突无法跨越与感觉神经移植物桥接的神经间隙(> 5 厘米长)再生,因为这种长移植物无法形成血管。随着患者年龄的增加,由于年龄相关的神经损伤诱导的血管生成减少,在长度增加的神经移植物中再生的轴突减少。当移植物被血管化时,轴突成功地穿过大鼠和临床上较长神经移植物。血管化在促进轴突再生中的作用可以通过在用血管内皮生长因子处理的神经移植物中发生的轴突再生来观察。锂通过激活 Wnt/(β)-catenin 通路在体内诱导血管生成。表明锂给药可能会增加感觉神经移植血管化,从而导致更广泛的轴突再生和功能恢复。锂触发促进轴突再生和增强神经恢复所需的细胞和分子机制。在生理剂量下,锂在动物模型和临床上诱导轴突再生,同时没有不良适应证。需要更广泛的研究来确定锂的给药是否会增强轴突再生和神经恢复的程度。

文章在《中国神经再生研究(英文版)》杂志2022年5月5期发表。

https://orcid.org/0000-0003-0928-7434 (Damien P. Kuffler) 

Abstract: The clinical “gold standard” technique for attempting to restore function to nerves with a gap is to bridge the gap with sensory autografts. However, autografts induce good to excellent recovery only across short nerve gaps, in young patients, and when repairs are performed a short time post nerve trauma. Even under the best of conditions, < 50% of patients recover good recovery. Although many alternative techniques have been tested, none is as effective as autografts. Therefore, alternative techniques are required that increase the percentage of patients who recover function and the extent of their recovery. This paper examines the actions of lithium, and how it appears to trigger all the cellular and molecular events required to promote axon regeneration, and how both in animal models and clinically, lithium administration enhances both the extent of axon regeneration and neurological recovery. The paper proposes more extensive clinical testing of lithium for its ability and reliability to increase the extent of axon regeneration and functional recovery. 

Key words: anastomosis, axon regeneration, lithium, nerve crush, nerve gaps, nerve repair, nerve trauma, neurological recovery, Schwann cells