Neural Regeneration Research ›› 2020, Vol. 15 ›› Issue (11): 2047-2056.doi: 10.4103/1673-5374.282266

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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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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