FK506 Induces Changes in Muscle Properties and Promotes Metabosensitive Nerve Fiber Regeneration
| Autor: | Tanguy Marqueste, Stéphane Garcia, Jean-François Chabas, Francois Feron, Olivier Alluin, Guy Magalon, Marie-Noëlle Lavaut, Guillaume Rao, Regis Legre, Patrick Decherchi |
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| Přispěvatelé: | Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN (NICN), Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée - Aix-Marseille 2, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de chirurgie de la main, chirurgie plastique et réparatrice des membres, Assistance Publique - Hôpitaux de Marseille (APHM), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2009 |
| Předmět: |
Male
Sensory Receptor Cells Growth Cones Nerve fiber Sensory system Pharmacology Neuroprotection Tacrolimus Potassium Chloride Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tibialis anterior muscle Peripheral Nerve Injuries medicine Animals Lactic Acid Peripheral Nerves 030304 developmental biology 0303 health sciences biology Chemistry Regeneration (biology) Peripheral Nervous System Diseases Peroneal Nerve Recovery of Function Anatomy Nerve Regeneration Rats Lactic acid Disease Models Animal Electrophysiology Treatment Outcome medicine.anatomical_structure Muscle Fibers Fast-Twitch biology.protein [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Neurology (clinical) Immunosuppressive Agents 030217 neurology & neurosurgery Neurotrophin |
| Zdroj: | Journal of Neurotrauma Journal of Neurotrauma, Mary Ann Liebert, 2009, 26 (1), pp.97-108. ⟨10.1089/neu.2008.0695⟩ Journal of Neurotrauma, 2009, 26 (1), pp.97-108. ⟨10.1089/neu.2008.0695⟩ |
| ISSN: | 1557-9042 0897-7151 |
| DOI: | 10.1089/neu.2008.0695 |
| Popis: | International audience; Abstract Accumulating evidence indicates that in addition to its immunosuppressant properties, FK506 (tacrolimus), an FDA-approved molecule, promotes nerve regeneration. However, the neuroprotective and neurotrophic effects of this molecule on sensitive fiber regeneration have never been studied. In order to fill this gap in our knowledge, we assessed the therapeutic potential of FK506 in a rat model of peripheral nerve repair. A 1-cm segment of left peroneal nerve was cut out and immediately autografted in an inverted position. After surgery, the animals were treated with FK506 (1.2 mg/kg/d) via an osmotic pump and compared to untreated animals. Recovery of use of the injured leg was assessed weekly for 12 weeks using a walking track apparatus and a camcorder. At the end of this period, motor and metabosensitive responses of the regenerated axons were recorded and histological analysis was performed. We observed that FK506 significantly: (1) increased the diameter of regenerated axons in the distal portion of the graft; (2) improved the responses of sensory neurons to metabolites such as potassium chloride and lactic acid; and (3) induced a fast-to-slow-fiber-type transition of the tibialis anterior muscle. Taken together, these data indicate that FK506 potentiates metabosensitive nerve fiber regeneration. Pharmacological studies of various dosages and concentrations of FK506 are required before recommending this drug for therapeutic treatment of nerve injuries. |
| Databáze: | OpenAIRE |
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