中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (2): 319-324.doi: 10.4103/1673-5374.290900

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

强制性运动可增强缺血性卒中损伤侧脑组织中α-氨基-3-羟基-5-甲基-4-异唑恶唑丙酸受体依赖性突触的可塑性

  

  • 出版日期:2021-02-15 发布日期:2020-12-03
  • 基金资助:

    国家自然科学基金项目(8187184181601960

Constraint-induced movement therapy enhances AMPA receptor-dependent synaptic plasticity in the ipsilateral hemisphere following ischemic stroke

Jian Hu#, Pei-Le Liu#, Yan Hua#, Bei-Yao Gao, Yu-Yuan Wang, Yu-Long Bai*, #br# Chan Chen*#br#   

  1. Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
  • Online:2021-02-15 Published:2020-12-03
  • Contact: Yu-Long Bai, dr_baiyl@fudan.edu.cn; Chan Chen, chanchen09@fudan.edu.cn. #These authors contributed equally to this study.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81871841 (to YLB) and 81601960 (to CC).

摘要:

强制性运动是一种通过促进卒中后突触可塑性,改善卒中后受损上肢运动功能恢复的有效方法。缺血性脑卒中后的强制性运动可增加患侧感觉运动皮质突触上α-氨基-3-羟基-5-甲基-4-异唑恶唑丙酸受体(AMPAR)的表达。由于AMPAR的分布是受到高度调控的,只有位于突触后膜上的AMPAR才具备介导突触传递的功能。因此,此次实验中模拟了缺血性卒中后突触膜表面AMPAR的表达。(1)以线栓法建立的大脑中动脉闭塞模型大鼠,从造模后第7天开始,进行为期2周的跑轮强制性运动强制性运动,每2d增加20min;(2)结果表明,强制性运动可增加损伤侧感觉运动皮质中含有GluR2的功能性突触,减少损伤侧感觉运动皮质和海马CA3区中缺少GluR2亚基的AMPAR的数量,还能增强损伤侧感觉运动皮质突触中AMPAR的表达以及损伤侧感觉运动皮质和海马中突触表面AMPAR的表达;(3)结果可证明强制性运动通过增强脑缺血大鼠损伤侧大脑中AMPAR介导的突触传递改善其运动功能。实验于2018年3月3日经复旦大学动物伦理委员会批准(批准号201802173S)。

https://orcid.org/0000-0003-0461-1506 (Yu-Long Bai);

https://orcid.org/0000-0001-7629-2028 (Chan Chen)

关键词: 脑, 卒中, 突触, 损伤, 修复, 再生, 可塑性, 实验

Abstract: Constraint-induced movement therapy (CIMT) can promote the recovery of motor function in injured upper limbs following stroke, which may be associated with upregulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) at synapses in the ipsilateral sensorimotor cortex in our previous study. However, AMPAR distribution is tightly regulated, and only AMPARs on the postsynaptic membrane can mediate synaptic transmission. We speculated that synaptic remodeling induced by movement-associated synaptic activity can promote functional recovery from stroke. To test this hypothesis, we compared AMPAR expression on the postsynaptic membrane surface in a rat model of ischemic stroke induced by middle cerebral artery occlusion (MCAO) with versus without CIMT, which consisted of daily running wheel training for 2 weeks starting on day 7 after MCAO. The results showed that CIMT increased the number of glutamate receptor (GluR)2-containing functional synapses in the ipsilateral sensorimotor cortex, and reduced non-GluR2 AMPARs in the ipsilateral sensorimotor cortex and hippocampal CA3 region. In addition, CIMT enhanced AMPAR expression on the surface of post-synaptic membrane in the ipsilateral sensorimotor cortex and hippocampus. Thus, CIMT promotes the recovery of motor function of injured upper limbs following stroke by enhancing AMPAR-mediated synaptic transmission in the ischemic hemisphere. These findings provide supporting evidence for the clinical value of CIMT for restoring limb movement in stroke patients. All experimental procedures and protocols were approved by the Department of Laboratory Animal Science of Fudan University, China (approval No. 201802173S) on March 3, 2018.

Key words: brain, experiment, injury, plasticity, regeneration, repair, stroke, synapse