FK506 induces changes in muscle properties and promotes metabosensitive nerve fiber regeneration.
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.
Chabas
Jean-François
JF
Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (UMR CNRS 6184), Université de la Méditerranée (Aix-Marseille II) , Faculté de Médecine Nord, Institut Fédératif de Recherche Jean Roche, Marseille, France.
Alluin
Olivier
O
Rao
Guillaume
G
Garcia
Stéphane
S
Lavaut
Marie-Noëlle
MN
Legré
Régis
R
Magalon
Guy
G
Marqueste
Tanguy
T
Feron
François
F
Decherchi
Patrick
P
D000818:Animals; D004195:Disease Models, Animal; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D019344:Lactic Acid / Q000819:agonists / Q000378:metabolism; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010543:Peroneal Nerve / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D011189:Potassium Chloride / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D019344:Lactic Acid; D011189:Potassium Chloride; D016559:Tacrolimus