Department of Biotechnology, School of Basic Science, Guangzhou Medical University, Guangzhou, China.
Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
J Reconstr Microsurg. 2014 Jul;30(6):381-8. doi: 10.1055/s-0034-1381751. Epub 2014 Jun 23.
Peripheral nerve injuries usually require a graft to facilitate axonal regeneration into the distal nerve stump. Acellular nerve grafts are good candidates for nerve repair, but clinical outcomes from grafts are not always satisfactory. Etifoxine is a ligand of the 18-kDa translocator protein (TSPO) and has been demonstrated to serve multiple functions in nervous system.
This study aimed to determine the optimal concentration of etifoxine for neurite outgrowth using PC12 cells and verify whether etifoxine could enhance in vivo peripheral nerve regeneration. PC12 cells were exposed to various concentrations of etifoxine (5, 10, 20, and 40 µM). Neuronal-like outgrowth and glia-derived neurotrophic factor (GDNF) mRNA expression were measured, and a rat sciatic nerve transection model was employed. Histological examination was used to evaluate the efficacy of nerve regeneration, and real-time polymerase chain reaction (PCR) evaluated changes in mRNA levels after etifoxine treatment.
Our data show that etifoxine increased neuronal-like outgrowth in PC12 cells in a dose-dependent manner; however, GDNF expression peaked at 20 µM etifoxine (1.97-fold increase compared with control, p = 0.0046). In vivo studies demonstrated that etifoxine improved sciatic nerve regeneration, modulated immune responses, and boosted neurotrophin expression.
Because of etifoxine's adverse effects, we suggest an optimal etifoxine concentration of 20 µM. Its beneficial role may lie in increased neurotrophin expression, and etifoxine may be a promising therapeutic for patients with peripheral nerve injuries.
周围神经损伤通常需要移植物来促进轴突再生到远端神经残端。去细胞神经移植物是神经修复的良好候选物,但移植物的临床效果并不总是令人满意。乙非西定是 18kDa 转位蛋白(TSPO)的配体,已被证明在神经系统中具有多种功能。
本研究旨在确定乙非西定促进 PC12 细胞轴突生长的最佳浓度,并验证乙非西定是否能增强周围神经再生。将 PC12 细胞暴露于不同浓度的乙非西定(5、10、20 和 40μM)中。测量神经元样突起和胶质衍生神经营养因子(GDNF)mRNA 的表达,并采用大鼠坐骨神经横断模型。组织学检查用于评估神经再生的效果,实时聚合酶链反应(PCR)评估乙非西定处理后 mRNA 水平的变化。
我们的数据表明,乙非西定以剂量依赖性方式增加 PC12 细胞中的神经元样突起;然而,GDNF 表达在 20μM 乙非西定时达到峰值(与对照组相比增加 1.97 倍,p=0.0046)。体内研究表明,乙非西定改善了坐骨神经再生,调节了免疫反应,并促进了神经营养因子的表达。
由于乙非西定的不良反应,我们建议使用 20μM 的最佳乙非西定浓度。其有益作用可能在于增加神经营养因子的表达,乙非西定可能是周围神经损伤患者的一种有前途的治疗方法。