中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (20): 1796-1809.doi: 10.4103/1673-5374.143424

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

失神经支配肌肉主要变化及对再生神经支配的影响

  

  • 收稿日期:2014-08-11 出版日期:2014-10-25 发布日期:2014-10-25

Key changes in denervated muscles and their impact on regeneration and reinnervation

Peng Wu 1, 2, 6, Aditya Chawla 1, 7, Robert J. Spinner 1, Cong Yu 2, Michael J. Yaszemski 3, Anthony J. Windebank 4, Huan Wang 1, 5   

  1. 1 Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
    2 Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, China
    3 Departments of Orthopedic Surgery and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
    4 Department of Neurology, Mayo Clinic, Rochester, MN, USA
    5 Shanghai Key Laboratory of Peripheral Nerve and Microsurgery, Shanghai, China
    6 Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
    7 Department of Orthopedic Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Received:2014-08-11 Online:2014-10-25 Published:2014-10-25
  • Contact: Huan Wang, M.D., Ph.D., Department of Neurologic Surgery, Mayo Clinic, 200 First Street SW Rochester, MN 55905, USA, wang.huan@mayo.edu.

摘要:

NMDA受体是离子型谷氨酸能受体中的一类,控制了许多谷氨酸突触的通讯。突触部位存在GluN2B的NMDA受体能保持活性连续的细胞交流,大量动物实验证据暗示存在GluN2B的NMDA受体(GluN2B-NMDA受体)诱导兴奋性毒性细胞死亡和β淀粉样蛋白(Aβ)突触功能障碍。因此,抑制GluN2B-NMDA受体被认为是阿尔茨海默氏病提供神经保护和改善认知功能的一个潜在治疗策略。然而目前,GluN2B拮抗剂对AD模型小鼠长期在体的治疗是否有效尚未见报道,这是评估GluN2B拮抗剂评估在阿尔茨海默病潜在治疗价值的关键。因此,北京大学深圳研究生院化生学院周强教授对美金刚(NMDA受体拮抗剂)作为中重度阿尔茨海默病靶向药物的治疗机制提出疑问。

Abstract:

The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle’s residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area,  and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair.