短暂电刺激可促进轴突再生,并促进小鼠神经横断和修复后的恢复。

Brief Electrical Stimulation Accelerates Axon Regeneration and Promotes Recovery Following Nerve Transection and Repair in Mice.

机构信息

Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.

出版信息

J Bone Joint Surg Am. 2021 Oct 20;103(20):e80. doi: 10.2106/JBJS.20.01965.

Abstract

BACKGROUND

Clinical outcomes following nerve injury repair can be inadequate. Pulsed-current electrical stimulation (ES) is a therapeutic method that facilitates functional recovery by accelerating axon regeneration. However, current clinical ES protocols involve the application of ES for 60 minutes during surgery, which can increase operative complexity and time. Shorter ES protocols could be a strategy to facilitate broader clinical adoption. The purpose of the present study was to determine if a 10-minute ES protocol could improve outcomes.

METHODS

C57BL/6J mice were randomized to 3 groups: no ES, 10 minutes of ES, and 60 minutes of ES. In all groups, the sciatic nerve was transected and repaired, and, in the latter 2 groups, ES was applied after repair. Postoperatively, changes to gene expression from dorsal root ganglia were measured after 24 hours. The number of motoneurons regenerating axons was determined by retrograde labeling at 7 days. Histomorphological analyses of the nerve were performed at 14 days. Function was evaluated serially with use of behavioral tests up to 56 days postoperatively, and relative muscle weight was evaluated.

RESULTS

Compared with the no-ES group, both ES groups demonstrated increased regeneration-associated gene expression within dorsal root ganglia. The 10-minute and 60-minute ES groups demonstrated accelerated axon regeneration compared with the no-ES group based on increased numbers of labeled motoneurons regenerating axons (mean difference, 202.0 [95% confidence interval (CI), 17.5 to 386.5] and 219.4 [95% CI, 34.9 to 403.9], respectively) and myelinated axon counts (mean difference, 559.3 [95% CI, 241.1 to 877.5] and 339.4 [95% CI, 21.2 to 657.6], respectively). The 10-minute and 60-minute ES groups had improved behavioral recovery, including on grid-walking analysis, compared with the no-ES group (mean difference, 11.9% [95% CI, 3.8% to 20.0%] and 10.9% [95% CI, 2.9% to 19.0%], respectively). There was no difference between the ES groups in measured outcomes.

CONCLUSIONS

A 10-minute ES protocol accelerated axon regeneration and facilitated functional recovery.

CLINICAL RELEVANCE

The brief (10-minute) ES protocol provided similar benefits to the 60-minute protocol in an acute sciatic nerve transection/repair mice model and merits further studies.

摘要

背景

神经损伤修复后的临床结果可能并不理想。脉冲电流电刺激(ES)是一种治疗方法,通过加速轴突再生来促进功能恢复。然而,目前的临床 ES 方案涉及在手术期间应用 ES 60 分钟,这会增加手术的复杂性和时间。较短的 ES 方案可能是促进更广泛临床应用的一种策略。本研究旨在确定 10 分钟 ES 方案是否可以改善结果。

方法

C57BL/6J 小鼠随机分为 3 组:无 ES 组、10 分钟 ES 组和 60 分钟 ES 组。在所有组中,坐骨神经均被横断并修复,在后 2 组中,修复后应用 ES。术后 24 小时测量背根神经节的基因表达变化。通过逆行标记在 7 天内确定再生轴突的运动神经元数量。在 14 天进行神经组织形态学分析。术后连续使用行为测试评估功能,直至 56 天,并评估相对肌肉重量。

结果

与无 ES 组相比,ES 两组在背根神经节中均表现出与再生相关的基因表达增加。与无 ES 组相比,10 分钟和 60 分钟 ES 组的运动神经元再生轴突的标记数量(平均差异,202.0[95%置信区间(CI),17.5 至 386.5]和 219.4[95%CI,34.9 至 403.9])和有髓轴突计数(平均差异,559.3[95%CI,241.1 至 877.5]和 339.4[95%CI,21.2 至 657.6])均增加,提示轴突再生加速。与无 ES 组相比,10 分钟和 60 分钟 ES 组的行为恢复更好,包括网格行走分析(平均差异,11.9%[95%CI,3.8%至 20.0%]和 10.9%[95%CI,2.9%至 19.0%])。ES 两组在测量结果方面没有差异。

结论

10 分钟 ES 方案加速了轴突再生并促进了功能恢复。

临床意义

在急性坐骨神经横断/修复小鼠模型中,短暂(10 分钟)ES 方案与 60 分钟方案提供了相似的益处,值得进一步研究。

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