中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (10): 2056-2063.doi: 10.4103/1673-5374.308099

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

亚甲蓝可促进聚乙二醇融合对大鼠完全横断坐骨神经的修复

  

  • 出版日期:2021-10-15 发布日期:2021-03-19
  • 基金资助:

    这项工作得到了美国国防部同行评审骨科研究计划奖的资助

Methylene blue enhances polyethylene glycol-fusion repair of completely severed rat sciatic nerves

Cameron L. Ghergherehchi1, Jaimie T. Shores2, Joseph Alderete3, Erik K. Weitzel3, George D. Bittner4, *   

  1. 1Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX, USA; 2Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Department of Surgery, RESTOR Laboratory, San Antonio, TX, USA; 4Department of Neuroscience, University of Texas at Austin, Austin, TX, USA
  • Online:2021-10-15 Published:2021-03-19
  • Contact: George D. Bittner, PhD, bittner@austin.utexas.edu.
  • Supported by:
    This work was supported by a grant from Department of Defense Peer Reviewed Orthopaedic Research Program award 
    (grant No. OR180077 W81XWH-19-2-0054; to GDB).

摘要:

周围神经完全切断会立即导致远端轴突介导的感觉知觉肌肉收缩和自行为的丧失。与可能最终使神经支配的目标神经失调的近端轴突自然再生(〜1mm /天)相反,聚乙二醇(PEG)融合可在几分钟之内恢复神经支配,融合由神经缝合以及低钙和等渗钙溶液、抗氧化剂亚甲蓝和膜融合聚乙二醇(PEG)。这项研究旨在观察无亚甲蓝(0%),0.5%或1%亚甲蓝的PEG融合对雌性大鼠坐骨神经中段完全断后自行为恢复的促进作用。通过坐骨神经功能指数(SFI)评估大鼠坐骨神经完全横断后后肢行为。发现与单独的PEG加神经合相比,在带有神经合的PEG融合方案中,将神经浸入无菌蒸馏水中的1%和0.5%亚甲蓝均可明显提高大鼠行为恢复的速度和程;且0.5%与1%亚甲蓝大鼠自主行为恢复的促进作用一样。由于无菌的1%亚甲蓝已不应用于临床,因此建议在即将进行的人类临床试验进一步评估包括0.5%亚甲蓝的PEG融合对周围神经修复的安全性和有效性。

https://orcid.org/0000-0002-5610-6264 (George D. Bittner)

Abstract: Complete transection of peripheral mixed nerves immediately produces loss of sensory perception, muscle contractions and voluntary behavior mediated by the severed distal axons. In contrast to natural regeneration (~1 mm/d) of proximal axons that may eventually reinnervate denervated targets, re-innervation is restored within minutes by PEG-fusion that consists of  neurorrhaphy and a sequence of well specified hypo- and isotonic calcium-free or calcium-containing solutions, the anti-oxidant methylene blue (MB) and the membrane fusogen polyethylene glycol (PEG). In this study, we examined the relative efficacy of PEG-fusion with no MB (0%), 0.5% MB, or 1% MB on the recovery of voluntary behaviors by female Sprague-Dawley rats with a complete mid-thigh severance of their sciatic nerve bathed in extracellular fluid or calcium-containing isotonic saline. The recovery of voluntary behaviors is the most relevant measure of success of any technique to repair peripheral nerve injuries. We assessed recovery by the sciatic functional index, a commonly used measure of voluntary hindlimb behaviors following complete sciatic transections. We reported that both 1% MB and 0.5% MB in sterile distilled water in our PEG-fusion protocol with neurorrhaphy significantly increased the rate and extent of behavioral recovery compared to PEG plus neurorrhaphy alone. Furthermore, 0.5% MB was as effective as 1% MB in voluntary behavioral recovery as assessed by the sciatic functional index. Since sterile 1% MB is no longer clinically available, we therefore recommend that 0.5% MB be included in upcoming human clinical trials to evaluate the safety and efficacy of PEG-fusion. All animal procedures were approved by the University of Texas Institutional Animal Care and Use Committee (AUP-2019-00225) on September 9, 2020.

Key words: axotomy, methylene blue, nerve repair, neurorrhaphy, peripheral nerve injury, polyethylene glycol fusion, sciatic nerve

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