Vitamin D2 Potentiates Axon Regeneration
Vitamin D2 Potentiates Axon Regeneration
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DOI：
10.1089/neu.2008.0593
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发表时间：
2008-10-01
影响因子：
4.2
通讯作者：
Feron, Francois
中科院分区：
文献类型：
--
作者：
Chabas, Jean-Francois;Alluin, Olivier;Feron, Francois
到目前为止，使用自体组织移植仍然是修复切断的周围神经的“金标准”技术。然而，恢复并不理想，需要神经活性分子。在目前的研究中，我们将注意力集中在维生素D上，这是一种FDA批准的分子，其神经保护和神经营养作用日益得到认可。我们评估了麦角钙化醇-维生素D的植物衍生形式，命名为维生素D-2-在周围神经损伤和修复的大鼠模型中的治疗潜力。切取左侧腓神经10 mm，立即倒置自体移植。手术后，动物接受麦角钙化醇(100IU/kg/天)治疗，并与未治疗的动物进行比较。在术后10周内，使用步行式跟踪器和数字摄像机每周测量后肢功能恢复情况。在此期间结束时，计算再生轴突的运动和敏感反应，并进行组织学分析。我们观察到，维生素D-2显著(I)增加轴突发生和轴突直径；(Ii)改善感觉神经元对如KCl和乳酸等代谢物的反应；(Iii)诱导胫前肌从快到慢的纤维型转变。此外，补充维生素D不会影响功能恢复。总而言之，这些数据表明维生素D促进轴突再生。现在需要对两种形式的维生素D(麦角钙化醇和胆钙化醇)进行不同浓度的药理学研究，然后才能推荐这种分子作为神经损伤后潜在的补充治疗方法。
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 D-2-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 D-2 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.