Rho-kinase inhibition enhances axonal regeneration after peripheral nerve injury
Rho-kinase inhibition enhances axonal regeneration after peripheral nerve injury
复制标题
DOI：
10.1111/j.1529-8027.2006.00091.x
复制
发表时间：
2006-09-01
影响因子：
3.8
通讯作者：
Yamashita, Toshihide
中科院分区：
文献类型：
--
作者：
Hiraga, Akiyuki;Kuwabara, Satoshi;Yamashita, Toshihide
在受损的成年神经元中，轴突再生和神经元功能重建的过程必须被激活。在这项研究中，我们评估了轴突延长的关键调节因子RhoA在周围神经系统损伤后是否被激活。小鼠坐骨神经损伤后，RhoA在运动神经元中被激活，但在雪旺细胞中不被激活。为了检验RhoA及其效应物Rho-Kinase的激活是否延缓了受损运动神经元的轴突再生，我们使用了Rho-Kinase抑制剂Fasudil。与对照组相比，法舒地尔治疗的小鼠轴突损伤后，远端诱发的复合肌肉动作电位的幅度显著增加。组织学分析显示，法舒地尔治疗增加了再生的大直径轴突的数量，提示抑制Rho-Kinase促进轴突成熟。此外，法舒地尔不抑制再生轴突的髓鞘形成。这些发现表明，RhoA/Rho-Kinase可能是促进人类周围神经病轴突再生的一个实用的分子靶点。
In injured adult neurons, the process of axonal regrowth and reestablishment of the neuronal function have to be activated. We assessed in this study whether RhoA, a key regulator of neurite elongation, is activated after injury to the peripheral nervous system. RhoA is activated in motoneurons but not in Schwann cells after mouse sciatic nerve injury. To examine whether the activation of RhoA and its effector, Rho-kinase, retards axon regeneration of injured motoneurons, we employed a Rho-kinase inhibitor, fasudil. Amplitudes of distally evoked compound muscle action potentials are increased significantly faster after axonal injury in mice treated with fasudil compared with controls. Histological analysis shows that fasudil treatment increases the number of regenerating axons with large diameter, suggesting that axon maturation is facilitated by Rho-kinase inhibition. In addition, fasudil does not suppress the myelination of regenerating axons. These findings suggest that RhoA/Rho-kinase may be a practical molecular target to enhance axonal regeneration in human peripheral neuropathies.