The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural regeneration after axotomy in the peripheral nervous system
The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural regeneration after axotomy in the peripheral nervous system
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DOI：
10.1097/01.prs.0000246380.40596.29
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发表时间：
2007-02-01
影响因子：
3.6
通讯作者：
Hosokawa, Ko
中科院分区：
文献类型：
--
作者：
Madura, Tomas;Kubo, Tateki;Hosokawa, Ko
背景资料：Rho家族的小GTP酶负责真核细胞中涉及肌动蛋白细胞骨架的各种过程，包括神经突生长。在周围神经损伤部位发现的几种物质被证明可以激活该家族的一个成员Rho。Rho的激活导致轴突生长抑制和创伤后神经病理性疼痛的发展。作者使用临床测试的Rho相关激酶抑制剂法舒地尔盐酸盐，以提高周围神经的功能恢复在大鼠。方法：在腓神经间置移植模型，作者管理法舒地尔（实验组）或盐水（对照组）（1）腹腔注射和（2）直接进入移植物通过显微注射（n = 6动物每个实验条件）。神经恢复进行了评估，在术后随访持续80天的腓神经功能指数，电生理，和histomorphometric analysis.Results：腓神经功能指数返回值没有显着不同的术前值在第55天（法舒地尔注射到移植物）和60（法舒地尔腹腔注射）在实验组。在对照组中，这需要70天（腹膜内注射盐水）和75天（将盐水注射到移植物中）。这些结果是支持电生理和组织形态学assessment.Conclusions：作者确定，盐酸法舒地尔能够加速周围神经轴突切断后的功能再生，这是一致的结果报告Rho级联中断中枢神经系统。由于盐酸法舒地尔是一种临床试验药物，它也可以用于增强人类患者的神经再生。
Background: The Rho family of small GTPases is responsible for various processes involving actin cytoskeleton in eukaryotic cells, including neurite outgrowth. Several substances found at the peripheral nerve injury site were shown to activate one member of this family, Rho. The activation of Rho leads to neurite outgrowth inhibition and the development of posttraumatic neuropathic pain. The authors used the clinically tested Rho-associated kinase inhibitor fasudil hydrochloride to enhance the functional recovery of the peripheral nerve in the rat.Methods: In the peroneal nerve interpositional graft model, the authors administered fasudil (experimental groups) or saline (control groups) (1) intraperitoneally and (2) directly into the graft by microinjection (n = 6 animals per experimental condition). Neural recovery was assessed during postoperative follow-up lasting 80 days by peroneal functional index, electrophysiologic, and histomorphometric analyses.Results: The peroneal functional index returned to values not significantly different from preoperative values on days 55 (fasudil injected into the graft) and 60 (fasudil injected intraperitoneally) in the experimental groups. In the control groups, this took 70 (saline injected intraperitoneally) and 75 days (saline injected into the graft). These results are supported by electrophysiologic and histomorphologic assessments.Conclusions: The authors determined that fasudil hydrochloride was capable of accelerating the functional regeneration after peripheral nerve axotomy, which is consistent with the results of reports about Rho cascade disruption in the central nervous system. Because fasudil hydrochloride is a clinically tested drug, it could be used to enhance neural regeneration in human patients as well.