Valproic acid enhances axonal regeneration and recovery of motor function after sciatic nerve axotomy in adult rats
Valproic acid enhances axonal regeneration and recovery of motor function after sciatic nerve axotomy in adult rats
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DOI：
10.1016/s0006-8993(03)02699-4
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发表时间：
2003-06-13
期刊：
影响因子：
2.9
通讯作者：
Zhang, X
中科院分区：
文献类型：
--
作者：
Cui, SS;Yang, CP;Zhang, X
最近已经证明，丙戊酸（VPA）强烈地促进神经突生长，激活细胞外信号调节激酶途径，并增加生长锥相关蛋白43和bcl-2水平在培养的人神经母细胞瘤SH-SY 5 Y细胞。我们假设VPA也可以增强成年动物的周围神经再生。为了验证这一假设，我们研究了VPA（300 mg/kg，每日一次，持续16周）对大鼠单次或条件性轴突切断术后坐骨神经轴突再生的影响。结果表明，VPA治疗组大鼠再生的有髓神经纤维和再神经支配的肌纤维总数均较未治疗组明显增加。如通过坐骨神经功能指数和脚趾伸展指数所测量的，接受单次轴突切断术而不接受VPA治疗的大鼠的神经再支配后肢的运动功能在第8周显著改善，并且在约第11周达到平台水平，而接受单一轴突切断加VPA治疗的大鼠和接受条件性轴突切断加或不加VPA治疗的大鼠的再神经支配后肢的运动功能在第4周显著改善第8周左右达到平台水平，后3组运动功能无显著性差异。结果表明，VPA能够促进成年大鼠坐骨神经再生和运动功能的恢复，提示VPA用于治疗人类周围神经损伤的潜在临床应用。(C)2003 Elsevier Science B. V.保留所有权利。
It has recently been demonstrated that valproic acid (VPA) robustly promotes neurite outgrowth, activates the extracellular signal regulated kinase pathway, and increases growth cone-associated protein 43 and bcl-2 levels in cultured human neuroblastoma SH-SY5Y cells. We hypothesized that VPA could also enhance peripheral nerve regeneration in adult animals. To test this hypothesis, we examined the effects of VPA (300 mg/kg daily for 16 weeks) on sciatic axonal regeneration following single or conditional axotomies in rats. The results showed that in VPA-treated rats there was a significant increase in the total numbers of regenerated myelinated nerve fibers and reinnervated muscle fibers in comparison with those rats not treated with VPA. As measured by sciatic function index and toe spread index, the motor function of the reinnervated hind limbs of rats receiving single axotomy without VPA treatment significantly improved at week 8 and reached plateau levels at about week 11, whereas the motor function of the reinnervated hind limbs of rats receiving single axotomy plus VPA and rats receiving conditional axotomy with or without VPA treatment significantly improved at week 4 and reached plateau levels at about week 8; there was no significant difference of the motor function among the three later groups. The results demonstrated that VPA is able to enhance sciatic nerve regeneration and recovery of motor function in adult rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans. (C) 2003 Elsevier Science B.V. All rights reserved.