Basic Research
Paired associative stimulation improves recovery of neurological function after cerebral infarction through modulating neuronal autophagy
Yinshan Lu, Xiujuan Zhang, Tiecheng Guo, Yan Hu, Xiangyu Zhang, Song Zhang
Published 2020-02-25
Cite as Chin J Phys Med Rehabil, 2020, 42(2): 105-111. DOI: 10.3760/cma.j.issn.0254-1424.2020.02.003
Abstract
ObjectiveTo investigate the effect of paired associative stimulation (PAS) on the recovery of neurological function after cerebral infarction, and to explore whether any such effect is associated with autophagy in the ischemic penumbra.
MethodsSixty adult male Sprague-Dawley rats were randomly divided into a sham operation group (n=20) and an experimental group (n=40). The rats of the experimental group underwent 90 minutes of right middle cerebral artery occlusion (MCAO), while the sham group received a sham operation. The experimental group was subsequently divided into a model group (n=20) and a PAS group (n=20). The PAS group received 14 days of paired associative stimulation (PAS) beginning 24 hours after the operation. Neurological dysfunction was evaluated with a modified neurological severity scale (mNSS) and the elevated body swing test (EBST) on the 1st, 7th and 14th day after the MCAO. The rats were then euthanized and the expression of LC3Ⅰ, LC3Ⅱ, Beclin1, and Cathepsin B in the ischemic penumbra were detected using Western blotting, while the distribution of LC3 in neurons was detected using double immunofluorescent staining.
ResultsCompared with the sham group, the average mNSS scores and EBST values of the model and PAS groups were both higher on the 7th and 14th day after the MCAO, with those of the PAS group significantly lower than those of the model group on those days. The average mNSS score on the 14th day was significantly lower than on the 7th day. Compared with the sham group, the average LC3Ⅱ/Ⅰ values, Beclin 1 and Cathepsin B levels of both the model group and the PAS group were significantly higher on the 7th and 14th day after the MCAO, with the LC3Ⅱ/Ⅰ values of the PAS group significantly lower than those of the model group at both time points. The PAS group also had significantly lower Beclin1 and Cathepsin B levels on day 14. On the 7th and 14th days after the MCAO, the average number of LC3-positive cells and the ratio of LC3-positive neurons to total neurons in the model and PAS groups were significantly greater than the those of sham group, with the PAS group′s values significantly lower than those of the model group at each time point.
ConclusionPAS can significantly promote neurological recovery after stroke. The beneficial effects may involve inhibition of neuronal autophagy in the ischemic penumbra.
Key words:
Cerebral infarction; Paired associative stimulation; Neuronal autophagy
Contributor Information
Yinshan Lu
Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Department of Rehabilitation Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China
Xiujuan Zhang
Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Department of Rehabilitation Medicine, Chengdu Second People′s Hospital, Chengdu 610011, China
Tiecheng Guo
Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Yan Hu
Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Department of Rehabilitation Medicine, Zhongnan Hospital, Wuhan University, Wuhan 430071, China
Xiangyu Zhang
Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Department of Rehabilitation Medicine, The 5th Hospital of Zhengzhou University, Zhengzhou 470000, China
Song Zhang
Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
