Electrical Stimulation Accelerates Axonal and Functional Peripheral Nerve Regeneration across Long Gaps
Electrical Stimulation Accelerates Axonal and Functional Peripheral Nerve Regeneration across Long Gaps
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DOI：
10.1089/neu.2010.1637
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发表时间：
2011-04-01
影响因子：
4.2
通讯作者：
Grothe, Claudia
中科院分区：
文献类型：
--
作者：
Haastert-Talini, Kirsten;Schmitte, Ruth;Grothe, Claudia
据报道，在进行腕管松解手术的动物模型和人类患者中，在端对端接合或小距离管状桥接之前对近端外周神经残端进行短期低频电刺激（ESTIM）可增加优先运动神经再支配和功能运动恢复。我们研究了ESTIM对大鼠坐骨神经间隙再生的影响，这些间隙超过了允许自发再生的距离。实验组采用三种不同的重建方法与ESTIM相结合。使用（I）神经自体移植、（II）差异填充硅胶管移植或（III）含有成纤维细胞生长因子-2过表达雪旺细胞（SC）的管状移植物移植进行基因治疗，桥接神经间隙（13 mm）。再生结果随访长达8周，并与非刺激对照组相比进行功能和组织形态学分析。结合ESTIM与神经自体移植显着增加再生神经中的神经纤维密度，以及腓肠肌电诊断记录检测到的功能恢复等级。ESTIM与幼稚SC移植的组合增加了间隙桥接神经组织的再生。尽管ESTIM与FGF-2（21/23-kD）基因治疗联合使用后宏观组织再生并未进一步改善，但后者导致再生神经在功能上重新连接到目标肌肉的比率很高。根据我们的研究结果，在人类患者的周围神经间隙重建的临床环境中，简短的ESTIM显示出加速轴突和功能（运动和感觉）结局的高潜力。
Short-term low-frequency electrical stimulation (ESTIM) of proximal peripheral nerve stumps prior to end-to-end coaptation or tubular bridging of small distances has been reported to increase preferential motor reinnervation and functional motor recovery in animal models and human patients undergoing carpal tunnel release surgery. We investigated the effects of ESTIM on regeneration across rat sciatic nerve gaps, which exceed distances that allow spontaneous regeneration. Three different reconstruction approaches were combined with ESTIM in the experimental groups. Nerve gaps (13mm) were bridged using (I) nerve autotransplantation, (II) transplantation of differentially filled silicone tubes, or (III) transplantation of tubular grafts containing fibroblast growth factor-2 overexpressing Schwann cells (SCs) for gene therapy. The regeneration outcome was followed for up to 8 weeks, and functionally as well as histomorphometrically analyzed in comparison to non-stimulated control groups. Combining ESTIM with nerve autotransplantation significantly increased the nerve fiber density in the regenerated nerve, and the grade of functional recovery as detected by electrodiagnostic recordings from the gastrocnemius muscle. The combination of ESTIM with transplantation of naive SCs increased the regeneration of gap-bridging nerve tissue. Although macroscopic tissue regeneration was not further improved after combining ESTIM with FGF-2(21/23-kD) gene therapy, the latter resulted in a high rate of regenerated nerves that functionally reconnected to the target muscle. Based on our results, brief ESTIM shows high potential to accelerate axonal as well as functional (motor and sensory) outcomes in the clinical setting of peripheral nerve gap reconstruction in human patients.