| Axonal Regeneration and Neuroinflammation: Roles for the Translocator Protein 18 kDa (TSPO). | |
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MedLine Citation:
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PMID: 21951109 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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After a traumatic injury of the nervous system or in the course of a neurodegenerative disease, the speed of axonal regeneration and the control of the inflammatory response are fundamental parameters of functional recovery. Spontaneous regeneration takes place in the peripheral nervous system, but the process is slow and often incomplete. There is currently no efficient treatment for enhancing axonal regeneration, including elongation speed and functional reinnervation. Ligands of the translocator protein 18 kDa (TSPO) are currently under investigation as therapeutic means for promoting neuroprotection, accelerating axonal regeneration and modulating inflammation. The mechanisms of action of TSPO ligands involve the regulation of mitochondrial activity and the stimulation of steroid biosynthesis. In the peripheral nervous system, TSPO expression is strongly upregulated after injury, primarily in Schwann cells and macrophages, but also in neurones. Its levels return to low control values when nerve regeneration is completed, strongly supporting an important role in regenerative processes. We have demonstrated a role for the benzoxazine etifoxine, in promoting axonal regeneration in the lesioned rat sciatic nerve, either after freeze-injury or complete transection. Etifoxine is already clinically approved for the treatment of anxiety disorders (Stresam®). Daily treatment with etifoxine resulted in a 2-fold acceleration in axonal regeneration, and in a marked improvement of both the speed and quality of functional recovery. Neuroregenerative effects of etifoxine are likely to be mediated by TSPO, and they may involve an increased synthesis of pregnenolone and its metabolites,such as progesterone. After freeze-injury of the sciatic nerve, administration of etifoxine also strongly reduced the number of activated macrophages and decreased the production of the inflammatory cytokines TNFα and IL1-β. Thus, this drug offers promise for the treatment of peripheral nerve injuries and axonal neuropathies. It may also be used as a lead compound in the development of new TSPO-based neuroprotective approaches. |
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Authors:
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Christelle Girard; Song Liu; David Adams; Catherine Lacroix; Marlène Sinéus; Céline Boucher; Vassilios Papadopoulos; Rainer Rupprecht; Michael Schumacher; Ghislaine Groyer |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-23 |
Journal Detail:
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Title: Journal of neuroendocrinology Volume: - ISSN: 1365-2826 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8913461 Medline TA: J Neuroendocrinol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Journal of Neuroendocrinology © 2011 Blackwell Publishing. |
Affiliation:
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UMR788 Inserm and University Paris-Sud 11, 80, rue du Général Leclerc, 94276 Kremlin-Bicêtre, France Department of Neurology, Bicêtre Hospital, Assistance Publique des Hôpitaux de Paris, 78 rue du Général Leclerc, 94276, Kremlin-Bicêtre, France The Research Institute of the McGill University Health Centre and Department of Medicine, Pharmacology and Therapeutics and Biochemistry, McGill University, 1650 Cedar Avenue, H3G 1A4, Montreal, Quebec, Canada Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, 80336 Munich, Germany Max-Planck-Institute of Psychiatry, 80804 Munich, Germany Department of Psychiatry and Psychotherapy, University Regensburg, 93053 Regensburg, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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