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

Ting Dai; Xiang Zhou; Yanan Li; Bo He; Zhaowei Zhu; Canbin Zheng; Shuang Zhu; Qingtang Zhu; Xiaolin Liu

doi:10.1055/s-0034-1381751

Journal of Reconstructive Microsurgery, Table of Contents

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

Authors

Ting Dai

¹Department of Biotechnology, School of Basic Science, Guangzhou Medical University, Guangzhou, China

^*These authors contributed equally to this work.
Xiang Zhou

²Department 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

³Department of Biochemistry & Molecular Biology, School of Basic Science, Guangzhou Medical University, Guangzhou, China
Bo He

²Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Zhaowei Zhu

²Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Canbin Zheng

²Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Shuang Zhu

²Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Qingtang Zhu

²Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
Xiaolin Liu

²Department of Microsurgery and Orthopaedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

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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References

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