Ultrasound therapy with optimal intensity facilitates peripheral nerve regeneration in rats through suppression of pro-inflammatory and nerve growth inhibitor gene expression
Ultrasound therapy with optimal intensity facilitates peripheral nerve regeneration in rats through suppression of pro-inflammatory and nerve growth inhibitor gene expression
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DOI：
10.1371/journal.pone.0234691
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发表时间：
2020-06-17
期刊：
影响因子：
3.7
通讯作者：
Kuroki, Hiroshi
中科院分区：
文献类型：
--
作者：
Ito, Akira;Wang, Tianshu;Kuroki, Hiroshi
背景治疗性超声（US）是一种很有前途的周围神经再生物理治疗方式。然而，有必要确定最有效的超声参数，并在其临床应用之前澄清潜在的机制。US强度是最重要的参数之一。然而，促进周围神经再生的最佳强度尚未确定。目的探讨超声（US）促进大鼠周围神经挤压伤后再生的最佳强度，并通过mRNA表达分析阐明其作用机制。方法建立成年刘易斯大鼠坐骨神经挤压伤模型，采用4种不同强度的超声照射：0（假刺激）、30、140和250 mW/cm 2，频率5d/周，持续时间5 min/d。我们在损伤后一周通过定量实时PCR评估周围神经再生。伤后3周进行组织形态计量学分析和运动功能分析。结果140 mW/cm（2）强度的超声刺激可促进轴突再生和出芽。mRNA表达显示，US抑制炎性细胞因子TNF和IL-6以及轴突生长抑制剂SEMA 3A和GSK 3 β的表达。结论：140 mW/cm（2）的强度是支持大鼠坐骨神经挤压伤后再生的最佳强度，部分原因是抑制了促炎和神经生长抑制因子基因的表达。
Background Therapeutic ultrasound (US) is a promising physical therapy modality for peripheral nerve regeneration. However, it is necessary to identify the most effective US parameters and clarify the underlying mechanisms before its clinical application. The intensity of US is one of the most important parameters. However, the optimum intensity for the promotion of peripheral nerve regeneration has yet to be determined. Objectives To identify the optimum intensity of US necessary for the promotion of peripheral nerve regeneration after crush injuries in rats and to clarify the underlying mechanisms of US by mRNA expression analysis. Methods We inflicted sciatic nerve crush injuries on adult Lewis rats and performed ultrasound irradiation using 4 different US intensities: 0 (sham stimulation), 30, 140, and 250 mW/cm(2)with frequency (5 days/week) and duration (5 min/day). We evaluated peripheral nerve regeneration by quantitative real-time PCR one week after injury. Histomorphometric analyses and motor function analysis were evaluated 3 weeks after injury. Results US stimulation enhanced re-myelination as well as sprouting of axons, especially at an intensity of 140 mW/cm(2). mRNA expression revealed that US suppressed the expression of the inflammatory cytokines TNF and IL-6 and the axonal growth inhibitors SEMA3A and GSK3 beta. Conclusions An intensity of 140 mW/cm(2)was optimal to support regeneration of the sciatic nerve after a crush injury in rats by, in part, the suppression of pro-inflammatory and nerve growth inhibitor gene expression.