Etifoxine promotes glia-derived neurite outgrowth in vitro and in vivo.

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.

• Authors: Ting Dai, Xiang Zhou, Yanan Li, Bo He, Zhaowei Zhu, Canbin Zheng, Shuang Zhu, Qingtang Zhu, Xiaolin Liu
• Journal: Journal of reconstructive microsurgery (J Reconstr Microsurg) Vol. 30 Issue 6 Pg. 381-8 (Jul 2014) ISSN: 1098-8947 [Electronic] United States
• PMID: 24956483 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Chemical References

• Glial Cell Line-Derived Neurotrophic Factor
• Interleukin-1
• Nerve Growth Factors
• Oxazines
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• etifoxine

Topics

• Animals
• Axons (drug effects, ultrastructure)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Glial Cell Line-Derived Neurotrophic Factor (genetics, metabolism)
• Interleukin-1 (genetics, metabolism)
• Microscopy, Electron, Transmission
• Models, Animal
• Nerve Growth Factors (metabolism)
• Nerve Regeneration (drug effects)
• Neurons (drug effects)
• Oxazines (administration & dosage)
• PC12 Cells
• RNA, Messenger (metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Sciatic Nerve (injuries, surgery, ultrastructure)
• Tumor Necrosis Factor-alpha (genetics, metabolism)