中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (11): 1968-1976.doi: 10.4103/1673-5374.259618

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

成对关联刺激可改善脑缺血后的突触可塑性和功能

  

  • 出版日期:2019-11-15 发布日期:2019-11-15
  • 基金资助:

    中国国家自然科学基金项目（81272156）

Paired associative stimulation improves synaptic plasticity and functional outcomes after cerebral ischemia

Yan Hu 1, 2 , Tie-Cheng Guo 1 , Xiang-Yu Zhang 1, 3 , Jun Tian 2 , Yin-Shan Lu 1   

  1. 1 Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei Province, China
    2 Department of Rehabilitation Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China
    3 Department of Rehabilitation Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
  • Online:2019-11-15 Published:2019-11-15
  • Contact: Tie-Cheng Guo, MD, pmr@tjh.tjmu.edu.cn.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81272156 (to TCG).

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摘要：

成对关联刺激作为一种新的无创性脑部刺激技术，结合了中枢经颅磁刺激与外周神经电刺激两种刺激手段，在调整两者之间的时间间隔可使成对关联刺激对大脑皮质的兴奋性产生不同的影响。(1)实验通过短暂性大脑中动脉闭塞建立脑缺血大鼠模型，在连续4周内给予90对频率为0.05Hz的成对关联刺激。以Morris水迷宫评估大鼠的空间学习和记忆能力，以透射电子显微镜和64通道多电极阵列观察大脑超微结构和突触可塑性的变化，以实时聚合酶链反应和蛋白质印迹检测海马中脑源性神经营养因子和N-甲基-D-天冬氨酸受体1的mRNA和蛋白质表达水平；(2)结果显示，经成对关联刺激治疗，脑缺血大鼠的学习记忆能力显著提高，海马CA1区突触的超微结构损伤明显恢复，海马CA3区和CA1区突触的长时程增强显著加强，且脑组织中脑源性神经营养因子和N-甲基-D-天冬氨酸受体1的mRNA和蛋白表达增加；(3)实验结果表明，成对关联刺激治疗可改善脑缺血的认知功能，且这种作用是通过增加脑源性神经营养因子和N-甲基-D-天冬氨酸受体1表达以及增强海马突触可塑性来实现的。动物实验于2015-07-11经华中科技大学同济医学院伦理委员会批准(批准号TJ-A20151102)。

orcid: 0000-0001-6271-6192(Tie-Cheng Guo)

关键词: 脑缺血, 成对关联刺激, 认知功能, 长时程增强, 突触可塑性, Morris水迷宫, 突触结构, N-甲基-D-天冬氨酸受体, 脑源性神经营养因子, 多电极阵列, 神经再生

Abstract:

Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cognition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China (approval No. TJ-A20151102) on July 11, 2015.

Key words: cerebral ischemia, paired associative stimulation, cognitive function, long-term potentiation, synaptic plasticity, Morris water maze, synaptic structure, N-methyl-D-aspartic acid receptor, brain-derived neurotrophic factor, multi-electrode array, neural regeneration