Abstract：
We recently demonstrated a repurposing beneficial effect of 4-aminopyridine (4-AP), a potassium channel blocker, on functional recovery and muscle atrophy after sciatic nerve crush injury in rodents. However, this effect of 4-AP is unknown in nerve transection, gap, and grafting models. To evaluate and compare the functional recovery, nerve morphology, and muscle atrophy, we used a novel stepwise nerve transection with gluing (STG), as well as 7-mm irreparable nerve gap (G-7/0) and 7-mm isografting in 5-mm gap (G-5/7) models in the absence and presence of 4-AP treatment. Following surgery, sciatic functional index was determined weekly to evaluate the direct in vivo global motor functional recovery. After 12 weeks, nerves were processed for whole-mount immunofluorescence imaging, and tibialis anterior muscles were harvested for wet weight and quantitative histomorphological analyses for muscle fiber cross-sectional area and minimal Feret\'s diameter. Average post-injury sciatic functional index values in STG and G-5/7 models were significantly greater than those in the G-7/0 model. 4-AP did not affect the sciatic functional index recovery in any model. Compared to STG, nerve imaging revealed more misdirected axons and distorted nerve architecture with isografting. While muscle weight, cross-sectional area, and minimal Feret\'s diameter were significantly smaller in G-7/0 model compared with STG and G-5/7, 4-AP treatment significantly increased right TA muscle mass, cross-sectional area, and minimal Feret\'s diameter in G-7/0 model. These findings demonstrate that functional recovery and muscle atrophy after peripheral nerve injury are directly related to the intervening nerve gap, and 4-AP exerts differential effects on functional recovery and muscle atrophy.
摘要：
我们最近证明了4-氨基吡啶（4-AP）的再利用有益作用，钾通道阻滞剂,对啮齿动物坐骨神经挤压伤后功能恢复和肌肉萎缩的影响。然而,4-AP的这种作用在神经横断中是未知的，间隙,和嫁接模型。为了评估和比较功能恢复，神经形态学,肌肉萎缩,我们使用了一种新型的带胶合的逐步神经横切术(STG)，以及在不存在和存在4-AP治疗的情况下，5-mm间隙（G-5/7）模型中的7-mm不可修复神经间隙（G-7/0）和7-mm等接枝。手术后,每周测定坐骨神经功能指数，以评估直接体内整体运动功能恢复。12周后,对神经进行整体免疫荧光成像处理，收集胫骨前肌进行湿重和肌纤维横截面积和最小Feret直径的定量组织形态学分析。STG和G-5/7模型的平均伤后坐骨神经功能指数值明显大于G-7/0模型。4-AP在任何模型中都不影响坐骨神经功能指数的恢复。与STG相比，神经成像显示更多的错误轴突和扭曲的神经结构与等接枝。虽然肌肉重量，横截面积,与STG和G-5/7相比，G-7/0模型中的最小Feret直径明显变小，4-AP处理显着增加了右TA肌肉质量，横截面积,和G-7/0型号的最小费雷特直径。这些结果表明，周围神经损伤后的功能恢复和肌肉萎缩与神经间隙的介入直接相关。和4-AP对功能恢复和肌肉萎缩有不同的影响。
