Vitamin D2 potentiates axon regeneration.
To date, the use of autograft tissue remains the "gold standard" technique for repairing transected peripheral nerves. However, the recovery is suboptimal, and neuroactive molecules are required. In the current study, we focused our attention on vitamin D, an FDA-approved molecule whose neuroprotective and neurotrophic actions are increasingly recognized. We assessed the therapeutic potential of ergocalciferol--the plant-derived form of vitamin D, named vitamin D2--in a rat model of peripheral nerve injury and repair. The left peroneal nerve was cut out on a length of 10 mm and immediately autografted in an inverted position. After surgery, animals were treated with ergocalciferol (100 IU/kg/day) and compared to untreated animals. Functional recovery of hindlimb was measured weekly, during 10 weeks post-surgery, using a walking track apparatus and a numerical camcorder. At the end of this period, motor and sensitive responses of the regenerated axons were calculated and histological analysis was performed. We observed that vitamin D2 significantly (i) increased axogenesis and axon diameter; (ii) improved the responses of sensory neurons to metabolites such as KCl and lactic acid; and (iii) induced a fast-to-slow fiber type transition of the Tibialis anterior muscle. In addition, functional recovery was not impaired by vitamin D supplementation. Altogether, these data indicate that vitamin D potentiates axon regeneration. Pharmacological studies with various concentrations of the two forms of vitamin D (ergocalciferol vs. cholecalciferol) are now required before recommending this molecule as a potential supplemental therapeutic approach following nerve injury.
Chabas
Jean-François
JF
Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, CNRS UMR 6184, Université de la Méditerranée, Service de Chirurgie de la Main, Hopitaux de Marseille, Marseille, France.
Alluin
Olivier
O
Rao
Guillaume
G
Garcia
Stéphane
S
Lavaut
Marie-Noëlle
MN
Risso
Jean Jacques
JJ
Legre
Régis
R
Magalon
Guy
G
Khrestchatisky
Michel
M
Marqueste
Tanguy
T
Decherchi
Patrick
P
Feron
François
F
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004594:Electrophysiology; D004872:Ergocalciferols / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000187:drug effects* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D020427:Peroneal Neuropathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology
D004872:Ergocalciferols; D018696:Neuroprotective Agents