中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (4): 731-738.doi: 10.4103/1673-5374.266925

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

去神经支配肌肉中残余神经肌肉接头有助于延迟周围神经修复后的功能恢复

  

  • 出版日期:2020-04-15 发布日期:2020-05-29
  • 基金资助:
    日本科学促进协会KAKENHI的支持;日本学生服务组织的资助

Remnant neuromuscular junctions in denervated muscles contribute to functional recovery in delayed peripheral nerve repair

Leyang Li1, Hiroyuki Yokoyama1, Hidetoshi Kaburagi1, Takashi Hirai1, Kunikazu Tsuji2, Mitsuhiro Enomoto1, Yoshiaki Wakabayashi1, Atsushi Okawa1   

  1. 1 Department of Orthopedic and Spinal Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    2 Department of Cartilage Regeneration, Tokyo Medical and Dental University, Tokyo, Japan
  • Online:2020-04-15 Published:2020-05-29
  • Contact: Mitsuhiro Enomoto, MD, PhD,enomorth@tmd.ac.jp.
  • Supported by:
    This work was supported by the Japan Society for the Promotion of Science KAKENHI (Grants 26462230 [to YM] and 16K10813 [to ME]) and grants from the Japan Student Services Organization (JASSO).

摘要:

长时间的周围神经损伤会诱发神经肌肉接头的退化和肌肉萎缩,从而导致不可逆的功能障碍。运动神经元轴突的再生取决于骨骼肌去神经支配的持续时间,因而有必要确定周围神经再生修复后的神经肌肉接头变性情况。实验横断thy1-YFP小鼠腓神经后,观察胫前肌失运动神经支配及行同种异体神经重建后的神经再生情况。发现胫前肌中的神经肌肉接头数量在术后4周维持在一定水平,然后在损伤后6周有所减少。相反,许旺细胞的数量在术后逐渐下降,在损伤后6周达到平台期。相较于术后6周进行延迟神经移植修复,术后4周延迟神经修复小鼠胫前肌中有更多数量的神经肌肉接头和更好的功能恢复。因此,作者认为周围神经损伤后4周内神经修复是周围神经外科修复较为适宜的时间点,残余的神经肌肉接头可能利于周围神经损伤后慢性期失神经肌肉的神经再生。

orcid: 0000-0001-8204-0185 (Mitsuhiro Enomoto)

关键词: 轴突, 同种异体神经, 神经肌肉接头, 周围神经损伤, 许旺细胞, 骨骼肌, 神经再生, 神经退行性疾病

Abstract: Schwann cell proliferation in peripheral nerve injury (PNI) enhances axonal regeneration compared to central nerve injury. However, even in PNI, long-term nerve damage without repair induces degeneration of neuromuscular junctions (NMJs), and muscle atrophy results in irreversible dysfunction. The peripheral regeneration of motor axons depends on the duration of skeletal muscle denervation. To overcome this difficulty in nerve regeneration, detailed mechanisms should be determined for not only Schwann cells but also NMJ degeneration after PNI and regeneration after nerve repair. Here, we examined motor axon denervation in the tibialis anterior muscle after peroneal nerve transection in thy1-YFP mice and regeneration with nerve reconstruction using allografts. The number of NMJs in the tibialis anterior muscle was maintained up to 4 weeks and then decreased at 6 weeks after injury. In contrast, the number of Schwann cells showed a stepwise decline and then reached a plateau at 6 weeks after injury. For regeneration, we reconstructed the degenerated nerve with an allograft at 4 and 6 weeks after injury, and evaluated functional and histological outcomes for 10 to 12 weeks after grafting. A higher number of pretzel-shaped NMJs in the tibialis anterior muscle and better functional recovery were observed in mice with a 4-week delay in surgery than in those with a 6-week delay. Nerve repair within 4 weeks after PNI is necessary for successful recovery in mice. Prevention of synaptic acetylcholine receptor degeneration may play a key role in peripheral nerve regeneration. All animal experiments were approved by the Institutional Animal Care and Use Committee of Tokyo Medical and Dental University on 5 July 2017, 30 March 2018, and 15 May 2019 (A2017-311C, A2018-297A, and A2019-248A), respectively.

Key words: axon, nerve allograft, nerve regeneration, neurodegeneration, neuromuscular junction, peripheral nerve injury, Schwann cell, skeletal muscle