Chen Yan, Wang Weidong, Zhao Zhimin, Ren Dong, Xin Danmou
Department of Hand Surgery, Wuhan Fourth Hospital, Puai Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
College of Life Science, Hubei Normal University, Huangshi, China.
Dose Response. 2020 Jan 21;18(1):1559325819899254. doi: 10.1177/1559325819899254. eCollection 2020 Jan-Mar.
4-AP-3-MeOH, a derivative of 4-aminopyridine, was developed and demonstrated to prevent nerve pulse diffusion due to myelin damage and significantly enhance axonal conduction following nerve injury. Currently, repurposing the existing drug such as 4-AP-3-MeOH to restore motor function is a promising and potential therapy of peripheral nerve injury. However, to evaluate drug effect on sciatic nerve injury is full of challenge.
Sciatic functional index was used to determine and measure the walking track in the stretch injury model. Nerve conductivity was performed by electrical stimulation of a nerve and recording the compound muscle action potential. Myelin thickness and regeneration was imaged and measured with transmission electron microscopy (TEM).
In this study, we developed a sciatic nerve injury model to minimize the spontaneous recovery mechanism and found that 4-AP-3-MeOH not only improved walking ability of the animals but also reduced the sensitivity to thermal stimulus. More interesting, 4-AP-3-MeOH enhanced and recovered electric conductivity of injured nerve; our TEM results indicated that the axon sheath thickness was increased and myelin was regenerated, which was an important evidence to support the recovery of injured nerve conductivity with 4-AP-3-MeOH treatment.
In summary, our studies suggest that 4-AP-3-MeOH is a viable and promising approach to the therapy of peripheral nerve injury and in support of repurposing the existing drug to restore motor function.
4-AP-3-MeOH是4-氨基吡啶的衍生物，已被研发并证明可防止因髓鞘损伤导致的神经脉冲扩散，并在神经损伤后显著增强轴突传导。目前，将4-AP-3-MeOH等现有药物重新用于恢复运动功能是一种有前景且有潜力的周围神经损伤治疗方法。然而，评估药物对坐骨神经损伤的效果充满挑战。
在拉伸损伤模型中，使用坐骨神经功能指数来确定和测量行走轨迹。通过电刺激神经并记录复合肌肉动作电位来进行神经传导性检测。用透射电子显微镜（TEM）对髓鞘厚度和再生情况进行成像和测量。
在本研究中，我们建立了一个坐骨神经损伤模型以尽量减少自发恢复机制，发现4-AP-3-MeOH不仅改善了动物的行走能力，还降低了对热刺激的敏感性。更有趣的是，4-AP-3-MeOH增强并恢复了受损神经的电传导性；我们的TEM结果表明轴突鞘厚度增加且髓鞘再生，这是支持4-AP-3-MeOH治疗可恢复受损神经传导性的重要证据。
总之，我们的研究表明4-AP-3-MeOH是一种可行且有前景的周围神经损伤治疗方法，支持将现有药物重新用于恢复运动功能。
