中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (11): 2047-2056.doi: 10.4103/1673-5374.282266

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

配对关联磁刺激促进大脑中脑闭塞模型中的神经修复

  

  • 出版日期:2020-11-15 发布日期:2020-08-19
  • 基金资助:

    国家自然科学基金(81974358, 81772453)

Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke

Bei-Yao Gao1, Cheng-Cheng Sun2 , Guo-Hua Xia3 , Shao-Ting Zhou4 , Ye Zhang2 , Ye-Ran Mao2 , Pei-Le Liu1 , Ya Zheng2 , Dan Zhao2 ,Xu-Tong Li4 , Janie Xu5 , Dong-Sheng Xu2 , Yu-Long Bai1#br#   

  1. 1 Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
    2 Rehabilitation Section, Department of Spine Surgery, Tongji Hospital, Medical School of Tongji University, Shanghai, China
    3 Department of Psychiatry and Behavioral Sciences, University of California, Davis, CA, USA
    4 Department of Neurology, Minhang Hospital Affiliated to Fudan University, Shanghai, China
    5 Brownell Talbot School, Omaha, NE, USA
  • Online:2020-11-15 Published:2020-08-19
  • Contact: Dong-Sheng Xu, PhD,dxu0927@tongji.edu.cn; Yu-Long Bai, PhD,dr_baiyl@fudan.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81974358, 81772453 (to DSX).

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摘要：

目前研究发现对脑卒中患者中采用配对关联磁刺激(Paired associative stimulation, PAS)可以促进功能恢复，但配对关联磁刺激的机制研究尚不明确。为此，实验将大鼠随机分为MCAO组和PAMS组，采用线栓法行大脑中动脉栓塞手术建立MCAO大鼠模型。在缺血第3天开始到第20天，PAMS组进行PAMS，MCAO组进行假刺激，每周3次。(1)在缺血后18 d内对大鼠进行错步实验，步行任务评估实验和平衡梁实验以检测大鼠行为学变化发现，与MCAO组相比，在缺血后第15天和第17天，PAMS组的大鼠均得到更好平衡功能评分，在缺血后第15天，PAMS组的患肢的错步率更低；(2)在缺血后第21天对大鼠进行安乐死，通过Western blot检测显示，PAMS组的大鼠损伤侧感觉运动皮质的神经可塑性相关蛋白BDNF，GluR2/3，PSD95和Synapsin-I表达明显增加；(3)静息态功能磁共振检测显示，在缺血后第20天，PAMS组大鼠损伤同侧半球感觉运动皮质的神经活动增加，而对侧半球减少；(4)实验提取大鼠大脑磁共振成像的结果生成大脑中动脉缺血大鼠3D脑模型，并运用有限元模拟电磁场分布显示，立体空间中电磁场分布在损伤侧皮质中比对侧皮质更集中，强度更高，最大值约为0.4 A/m2；(5)上述数据显示，PAMS可促进MCAO大鼠患侧感觉运动皮质脑区神经可塑性相关蛋白的表达上调，神经活动增加以及神经功能恢复。

orcid: 0000-0002-8477-5377 (Dong-Sheng Xu) 

         0000-0003-0461-1506 (Yu-Long Bai)

关键词: 脑源性神经营养因子, 有限元模拟, 谷氨酸受体, 同侧半球, 配对相关磁刺激, PSD-95, 静息态功能MRI, 卒中, 突触蛋白I, 经颅磁刺激

Abstract: Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model (MCAO) and paired associated magnetic stimulation (PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments—the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the foot- fault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m 2 , in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.

Key words: brain-derived neurotrophic factor, finite element simulation, glutamate receptor, ipsilateral hemisphere, paired associative stimulation, PSD95, resting-state functional MRI, stroke, synapsin I, transcranial magnetic stimulation