Etifoxine improves peripheral nerve regeneration and functional recovery
Open Access
- 23 December 2008
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (51), 20505-20510
- https://doi.org/10.1073/pnas.0811201106
Abstract
Peripheral nerves show spontaneous regenerative responses, but recovery after injury or peripheral neuropathies (toxic, diabetic, or chronic inflammatory demyelinating polyneuropathy syndromes) is slow and often incomplete, and at present no efficient treatment is available. Using well-defined peripheral nerve lesion paradigms, we assessed the therapeutic usefulness of etifoxine, recently identified as a ligand of the translocator protein (18 kDa) (TSPO), to promote axonal regeneration, modulate inflammatory responses, and improve functional recovery. We found by histologic analysis that etifoxine therapy promoted the regeneration of axons in and downstream of the lesion after freeze injury and increased axonal growth into a silicone guide tube by a factor of 2 after nerve transection. Etifoxine also stimulated neurite outgrowth in PC12 cells, and the effect was even stronger than for specific TSPO ligands. Etifoxine treatment caused a marked reduction in the number of macrophages after cryolesion within the nerve stumps, which was rapid in the proximal and delayed in the distal nerve stumps. Functional tests revealed accelerated and improved recovery of locomotion, motor coordination, and sensory functions in response to etifoxine. This work demonstrates that etifoxine, a clinically approved drug already used for the treatment of anxiety disorders, is remarkably efficient in promoting acceleration of peripheral nerve regeneration and functional recovery. Its possible mechanism of action is discussed, with reference to the neurosteroid concept. This molecule, which easily enters nerve tissues and regulates multiple functions in a concerted manner, offers promise for the treatment of peripheral nerve injuries and axonal neuropathies.Keywords
This publication has 39 references indexed in Scilit:
- Stathmin Family Protein SCG10 Differentially Regulates the Plus and Minus End Dynamics of Microtubules at Steady State in Vitro: Implications for Its Role in Neurite OutgrowthBiochemistry, 2007
- Ro5-4864, a synthetic ligand of peripheral benzodiazepine receptor, reduces aging-associated myelin degeneration in the sciatic nerve of male ratsMechanisms of Ageing and Development, 2005
- Role of the peripheral benzodiazepine receptor in sensory neuron regenerationMolecular and Cellular Neuroscience, 2005
- Ro5-4864, a peripheral benzodiazepine receptor ligand, reduces reactive gliosis and protects hippocampal hilar neurons from kainic acid excitotoxicityJournal of Neuroscience Research, 2005
- Role of thyroid hormones and their receptors in peripheral nerve regenerationJournal of Neurobiology, 1999
- [Treatment of adjustment disorder with anxiety: efficacy and tolerance of etifoxine in a double-blind controlled study].1999
- Neurofilament-dependent Radial Growth of Motor Axons and Axonal Organization of Neurofilaments Does Not Require the Neurofilament Heavy Subunit (NF-H) or Its PhosphorylationThe Journal of cell biology, 1998
- Neurosteroids: of the nervous system, by the nervous system, for the nervous system.1997
- Enhanced expression of the peripheral benzodiazepine receptor (PBR) and its endogenous ligand octadecaneuropeptide (ODN) in the regenerating adult rat sciatic nerveNeuroscience Letters, 1996
- Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervationJournal of Neuroscience, 1995