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J Reconstr Microsurg 2014; 30(06): 381-388
DOI: 10.1055/s-0034-1381751
Original Article WSRM 2013 Scientific Paper
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Etifoxine Promotes Glia-Derived Neurite Outgrowth In Vitro and In Vivo

Ting Dai
1   Department of Biotechnology, School of Basic Science, Guangzhou Medical University, Guangzhou, China
*   These authors contributed equally to this work.
,
Xiang Zhou
2   Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
*   These authors contributed equally to this work.
,
Yanan Li
3   Department of Biochemistry & Molecular Biology, School of Basic Science, Guangzhou Medical University, Guangzhou, China
,
Bo He
2   Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
,
Zhaowei Zhu
2   Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
,
Canbin Zheng
2   Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
,
Shuang Zhu
2   Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
,
Qingtang Zhu
2   Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
,
Xiaolin Liu
2   Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
› Author Affiliations
Further Information

Publication History

24 October 2013

08 April 2014

Publication Date:
23 June 2014 (online)

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Abstract

Background 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.

Methods 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.

Results 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.

Conclusions 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.

Keywords

etifoxine - GDNF - neurite outgrowth
 

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