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Yuan L, Wang Y, Hu X, Zuo Y, Jin T, Li X, Li X, Cheng L, Zhang H, Zhang T. Time-of-Day-Dependent Effects of Rehabilitation on Motor Recovery After Experimental Focal Cerebral Ischemia. Stroke 2025. [PMID: 40276875 DOI: 10.1161/strokeaha.125.050084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/19/2025] [Accepted: 04/11/2025] [Indexed: 04/26/2025]
Abstract
BACKGROUND Rehabilitation is an efficacious method to improve poststroke motor dysfunction. Various rehabilitative techniques have become popular in this field of research. However, it has not been reported whether better outcomes can be achieved if rehabilitation training is conducted at the optimal time of the day. METHODS A model of photothrombotic ischemic stroke was used in C57/BL6 mice, and poststroke 24-hour activity cycles were evaluated. We found an activity peak around Zeitgeber time (ZT)13 (21:00) and a trough around ZT20 (04:00) during the dark phase. In addition, we selected ZT6 (14:00) as the daytime training group (corresponding to the ZT13 training group, ZT20 training group, and ZT6 training group, respectively). The 3 groups underwent treadmill training for 4 weeks. Functional and histological recovery levels were compared among groups. In addition, bulk RNA sequencing analysis was used to explore the possible molecular mechanisms. RESULTS The results showed that stroke-induced mice maintained a regular nocturnal locomotor rhythm with reduced amplitude. Motor recovery was greater in the ZT13 training group than in the ZT6 group, with a trend toward better outcomes at ZT13 than ZT20. The ZT13 group also showed superior neuronal survival and neurogenesis compared with ZT6, while improvements between ZT13 and ZT20 were less pronounced. Bulk RNA sequencing suggested that synaptic plasticity, calcium signaling, cAMP signaling, and MAPK signaling pathways contributed to neural repair differences between ZT13 and ZT6. In addition, the results showed a similar pattern of motor recovery in female and aged mice trained at ZT13 compared with ZT6, reinforcing the benefits of time-of-day training. CONCLUSIONS In conclusion, rehabilitative training during the most active phase is beneficial for enhanced recovery outcomes. Our study suggests that rehabilitation should be conducted when the body is in an optimal physiological state-that is, a time-of-day-dependent rehabilitation strategy.
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Affiliation(s)
- Linran Yuan
- Qilu Hospital of Shandong University, Jinan, China (L.Y., T.Z.)
- China Rehabilitation Research Center, Beijing Bo'ai Hospital (L.Y., Y.W., X.H., Xudong Li, Xingzhu Li, L.C., H.Z., T.Z.)
- School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China (L.Y., T.Z.)
| | - Yunlei Wang
- China Rehabilitation Research Center, Beijing Bo'ai Hospital (L.Y., Y.W., X.H., Xudong Li, Xingzhu Li, L.C., H.Z., T.Z.)
| | - Xueyan Hu
- China Rehabilitation Research Center, Beijing Bo'ai Hospital (L.Y., Y.W., X.H., Xudong Li, Xingzhu Li, L.C., H.Z., T.Z.)
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China (X.H., Xudong Li, Xingzhu Li, L.C., T.Z.)
| | - Yao Zuo
- Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China (Y.Z.)
| | - Tianyu Jin
- Department of Rehabilitation Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, China (T.J.)
| | - Xudong Li
- China Rehabilitation Research Center, Beijing Bo'ai Hospital (L.Y., Y.W., X.H., Xudong Li, Xingzhu Li, L.C., H.Z., T.Z.)
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China (X.H., Xudong Li, Xingzhu Li, L.C., T.Z.)
| | - Xingzhu Li
- China Rehabilitation Research Center, Beijing Bo'ai Hospital (L.Y., Y.W., X.H., Xudong Li, Xingzhu Li, L.C., H.Z., T.Z.)
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China (X.H., Xudong Li, Xingzhu Li, L.C., T.Z.)
| | - Lingna Cheng
- China Rehabilitation Research Center, Beijing Bo'ai Hospital (L.Y., Y.W., X.H., Xudong Li, Xingzhu Li, L.C., H.Z., T.Z.)
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China (X.H., Xudong Li, Xingzhu Li, L.C., T.Z.)
| | - Haojie Zhang
- China Rehabilitation Research Center, Beijing Bo'ai Hospital (L.Y., Y.W., X.H., Xudong Li, Xingzhu Li, L.C., H.Z., T.Z.)
| | - Tong Zhang
- Qilu Hospital of Shandong University, Jinan, China (L.Y., T.Z.)
- China Rehabilitation Research Center, Beijing Bo'ai Hospital (L.Y., Y.W., X.H., Xudong Li, Xingzhu Li, L.C., H.Z., T.Z.)
- School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China (L.Y., T.Z.)
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China (X.H., Xudong Li, Xingzhu Li, L.C., T.Z.)
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Tu G, Jiang N, Chen W, Liu L, Hu M, Liao B. The neurobiological mechanisms underlying the effects of exercise interventions in autistic individuals. Rev Neurosci 2025; 36:27-51. [PMID: 39083671 DOI: 10.1515/revneuro-2024-0058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 07/15/2024] [Indexed: 08/02/2024]
Abstract
Autism spectrum disorder is a pervasive and heterogeneous neurodevelopmental condition characterized by social communication difficulties and rigid, repetitive behaviors. Owing to the complex pathogenesis of autism, effective drugs for treating its core features are lacking. Nonpharmacological approaches, including education, social-communication, behavioral and psychological methods, and exercise interventions, play important roles in supporting the needs of autistic individuals. The advantages of exercise intervention, such as its low cost, easy implementation, and high acceptance, have garnered increasing attention. Exercise interventions can effectively improve the core features and co-occurring conditions of autism, but the underlying neurobiological mechanisms are unclear. Abnormal changes in the gut microbiome, neuroinflammation, neurogenesis, and synaptic plasticity may individually or interactively be responsible for atypical brain structure and connectivity, leading to specific autistic experiences and characteristics. Interestingly, exercise can affect these biological processes and reshape brain network connections, which may explain how exercise alleviates core features and co-occurring conditions in autistic individuals. In this review, we describe the definition, diagnostic approach, epidemiology, and current support strategies for autism; highlight the benefits of exercise interventions; and call for individualized programs for different subtypes of autistic individuals. Finally, the possible neurobiological mechanisms by which exercise improves autistic features are comprehensively summarized to inform the development of optimal exercise interventions and specific targets to meet the needs of autistic individuals.
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Affiliation(s)
- Genghong Tu
- Department of Sports Medicine, 47878 Guangzhou Sport University , Guangzhou, Guangdong, 510500, P.R. China
- Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, 47878 Scientific Research Center, Guangzhou Sport University , Guangzhou, Guangdong, 510500, P.R. China
| | - Nan Jiang
- Graduate School, 47878 Guangzhou Sport University , Guangzhou, Guangdong, 510500, P.R. China
| | - Weizhong Chen
- Graduate School, 47878 Guangzhou Sport University , Guangzhou, Guangdong, 510500, P.R. China
| | - Lining Liu
- Graduate School, 47878 Guangzhou Sport University , Guangzhou, Guangdong, 510500, P.R. China
| | - Min Hu
- Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, 47878 Scientific Research Center, Guangzhou Sport University , Guangzhou, Guangdong, 510500, P.R. China
| | - Bagen Liao
- Department of Sports Medicine, 47878 Guangzhou Sport University , Guangzhou, Guangdong, 510500, P.R. China
- Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, 47878 Scientific Research Center, Guangzhou Sport University , Guangzhou, Guangdong, 510500, P.R. China
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Choi IA, Yun JH, Lee J, Choi DH. Neuropeptide FF Promotes Neuronal Survival and Enhances Synaptic Protein Expression Following Ischemic Injury. Int J Mol Sci 2024; 25:11580. [PMID: 39519132 PMCID: PMC11546865 DOI: 10.3390/ijms252111580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 10/25/2024] [Accepted: 10/26/2024] [Indexed: 11/16/2024] Open
Abstract
This study explores the neuroprotective effects of neuropeptide FF (NPFF, FLFQPQRFamide) in the context of ischemic injury. Based on transcriptomic analysis in stroke models treated with 5-Aza-dC and task-specific training, we identified significant gene expression changes, particularly involving NPFF. To further explore NPFF's role in promoting neuronal recovery, recombinant NPFF protein (rNPFF) was used in primary mixed cortical cultures subjected to oxygen-glucose deprivation and reoxygenation. Our results demonstrated that rNPFF significantly reduced lactate dehydrogenase release, indicating decreased cellular damage. It also significantly increased the expression of TUJ1 and MAP2, markers of neuronal survival and dendritic integrity. Additionally, rNPFF significantly upregulated key synaptic proteins, including GAP43, PSD95, and synaptophysin, which are essential for synaptic repair and plasticity. Post-injury rNPFF treatment led to a significant upregulation of pro-brain-derived neurotrophic factor (BDNF) and mature BDNF, which play critical roles in neuronal survival, growth, and synaptic plasticity. Moreover, rNPFF activated the protein kinase Cε isoform, Sirtuin 1, and peroxisome proliferator-activated receptor gamma pathways, which are crucial for regulating cellular stress responses, synaptic plasticity, and energy homeostasis, further promoting neuronal survival and recovery. These findings suggest that rNPFF may play a pivotal role in enhancing neuronal survival and synaptic plasticity after ischemic injury, highlighting its potential as a therapeutic target for stroke recovery.
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Affiliation(s)
- In-Ae Choi
- Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Republic of Korea; (I.-A.C.); (J.H.Y.); (J.L.)
- Department of Occupational Therapy, Division of Health, Baekseok University, Cheonan-si 31065, Chung-cheongnam-do, Republic of Korea
| | - Ji Hee Yun
- Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Republic of Korea; (I.-A.C.); (J.H.Y.); (J.L.)
| | - Jongmin Lee
- Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Republic of Korea; (I.-A.C.); (J.H.Y.); (J.L.)
- Department of Rehabilitation Medicine, Konkuk University School of Medicine, Konkuk University, Seoul 05029, Republic of Korea
| | - Dong-Hee Choi
- Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Republic of Korea; (I.-A.C.); (J.H.Y.); (J.L.)
- Department of Medical Science, Konkuk University School of Medicine, Konkuk University, Seoul 05029, Republic of Korea
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Liu S, Yang Y, Wang K, Zhang T, Luo J. A study on the impact of acute exercise on cognitive function in Alzheimer's disease or mild cognitive impairment patients: A narrative review. Geriatr Nurs 2024; 59:215-222. [PMID: 39053163 DOI: 10.1016/j.gerinurse.2024.06.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 05/28/2024] [Accepted: 06/21/2024] [Indexed: 07/27/2024]
Abstract
This narrative review follows the JBI approach and comprehensively explores the effects and mechanisms of acute exercise on cognitive function in Alzheimer's disease (AD) and Mild cognitive impairment (MCI) patients. The results showed that the combination of acute exercise and cognitive training improved the cognitive function of AD patients better than aerobic exercise or resistance training alone. For patients with MCI, moderate intensity acute aerobic exercise and resistance exercise were beneficial to enhance Inhibitory control (IC), but high-intensity acute exercise was adverse to improve IC; Brain-derived neurotrophic factor (BDNF) and Insulin-like growth factor 1 (IGF-1) may assume the potential mediating mechanism of acute exercise on cognitive function in AD and MCI patients, but more research is needed to further confirm this mechanism.
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Affiliation(s)
- Shiqi Liu
- Research Centre for Exercise Detoxification, College of Physical Education, Southwest University, Chongqing, 400715, China
| | - Yi Yang
- Research Centre for Exercise Detoxification, College of Physical Education, Southwest University, Chongqing, 400715, China
| | - Kun Wang
- Research Centre for Exercise Detoxification, College of Physical Education, Southwest University, Chongqing, 400715, China
| | - Tingran Zhang
- Research Centre for Exercise Detoxification, College of Physical Education, Southwest University, Chongqing, 400715, China
| | - Jiong Luo
- Research Centre for Exercise Detoxification, College of Physical Education, Southwest University, Chongqing, 400715, China
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Liu L, Chen S, Liang S, Liang Z. The expression profile of brain-derived exosomal miRNAs reveals the key molecules responsible for spontaneous motor function recovery in a rat model with permanent middle cerebral artery occlusion. Mamm Genome 2024; 35:362-376. [PMID: 38997467 DOI: 10.1007/s00335-024-10052-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 07/02/2024] [Indexed: 07/14/2024]
Abstract
The analysis of alterations in the expression and functionality of brain-derived exosomal miRNAs within ischemic stroke lesions provides significant insights into the mechanisms that contribute to disease recovery. We assessed spontaneous motor function in a rat model of permanent middle cerebral artery occlusion (pMCAO) using motor function scores and magnetic resonance imaging (MRI). Brain-derived exosomes from the infarcted brain tissue of the animal model were extracted and high-throughput sequencing of them was performed followed by bioinformatics analysis for differentially expressed miRNAs target genes. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to measure expression levels of differentially expressed miRNAs at various time points. The oxygen-glucose deprivation (OGD) model was established to investigate gene function through the assessment of cell proliferation and apoptosis using EdU proliferation and JC-1 apoptosis assay. The rat model demonstrated a spontaneous recovery of motor function and a reduction in cerebral infarction area from day 1 to day 14 post-operation. Over the course of the recovery period, miR-24-3p, miR-129-1-3p, and miR-212-5p maintained consistent expression levels, reaching their peak on the initial day following surgery. In the cell model, EdU detection indicated that miR-129-1-3p promoted cellular proliferation, while JC-1 detection revealed its suppressive impact on cellular apoptosis. The current research findings indicated the presence of spontaneous motor function restoration in a rat model of ischemic stroke. MiR-24-3p, miR-129-1-3p, and miR-212-5p were identified as pivotal genes in this recovery process, with miR-129-1-3p potentially influencing the restoration of spontaneous motor function in ischemic stroke through the regulation of neuronal proliferation and apoptosis.
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Affiliation(s)
- Liuyu Liu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Shengri Chen
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Shuolin Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Zhijian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.
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Zhou Y, Ren H, Hou X, Dong X, Zhang S, Lv Y, Li C, Yu L. The effect of exercise on balance function in stroke patients: a systematic review and meta-analysis of randomized controlled trials. J Neurol 2024; 271:4751-4768. [PMID: 38834700 DOI: 10.1007/s00415-024-12467-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 05/21/2024] [Accepted: 05/22/2024] [Indexed: 06/06/2024]
Abstract
OBJECTIVE A growing body of studies has examined the effect of exercise on balance function in stroke patients, with conflicting findings. This study aimed to investigate the effect of exercise on balance function in stroke patients and to determine the optimal exercise prescription for stroke patients. METHODS We conducted an extensive search across various databases, including PubMed, Web of Science, EBSCO, Cochrane, and Scopus. The search was conducted until March 11th, 2024. Data were pooled using the weighted mean difference (WMD) and 95% confidence interval. RESULTS Twenty-nine studies fulfilled the inclusion criteria. Exercise significantly improved Berg balance scale (BBS, WMD, 5.24, P < 0.00001) and timed up and go test (TUG, WMD, - 2.91, P < 0.00001) in stroke patients. Subgroup analyses showed that aerobic exercise (WMD, 6.71, P = 0.003), exercise conducted ≥ 8 weeks (WMD, 6.43, P < 0.00001), > 3 times per week (WMD, 6.18, P < 0.00001), ≥ 60 min per session (WMD, 6.40, P < 0.0001), and ≥ 180 min per week (WMD, 7.49, P < 0.00001) were more effective in improving BBS. CONCLUSIONS Exercise improved balance function in stroke patients, and aerobic exercise might be the most effective intervention. To improve balance function, this meta-analysis provides clinicians with evidence to recommend that stroke patients participate in a minimum of 8 weeks of exercise at least 3 times per week for more than 60 min per session, with a goal of 180 min per week being achieved by increasing the frequency of exercise.
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Affiliation(s)
- Yilun Zhou
- Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, China
- Department of Strength and Conditioning Assessment and Monitoring, Beijing Sport University, Beijing, China
| | - Hao Ren
- Department of Strength and Conditioning Assessment and Monitoring, Beijing Sport University, Beijing, China
| | - Xiao Hou
- School of Sport Sciences, Beijing Sport University, Beijing, China
| | - Xiaosheng Dong
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- National Health Commission of China Key Lab of Health Economics and Policy Research, Shandong University, Jinan, China
| | - Shiyan Zhang
- Department of Strength and Conditioning Assessment and Monitoring, Beijing Sport University, Beijing, China
| | - Yuanyuan Lv
- China Institute of Sport and Health Science, Beijing Sport University, Beijing, China
| | - Cui Li
- School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
| | - Laikang Yu
- Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, China.
- Department of Strength and Conditioning Assessment and Monitoring, Beijing Sport University, Beijing, China.
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Ranjbar K, Komaki A, Fayazi B, Zarrinkalam E. Coenzyme Q10 and exercise training reinstate middle cerebral artery occlusion-induced behavioral deficits and hippocampal long-term potentiation suppression in aging rats. Psychopharmacology (Berl) 2024; 241:1577-1594. [PMID: 38627309 DOI: 10.1007/s00213-024-06583-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 03/29/2024] [Indexed: 06/15/2024]
Abstract
RATIONAL Patients experience post-stroke cognitive impairment during aging. To date, no specific treatment solution has been reported for this disorder. OBJECTIVE The purpose of this study was to evaluate the effects of exercise training and coenzyme Q10 supplementation on middle cerebral artery occlusion (MCAO) induced behavioral impairment, long-term potentiation inhibition and cerebral infarction size in aging rats. METHODS Fifty aging male rats underwent MCAO surgery and were randomly distributed in to the following groups: 1-Sham, 2- control, 3- Coenzyme Q10, 4- Exercise training and 5- Exercise training with Q10 supplementation (Ex + Q10). Aerobic training groups were allowed to run on a treadmill for 12 weeks. Q10 (50 mg/kg) was administered intragastrically by gavage. Morris water maze, shuttle box and elevated plus maze tests were used to evaluate cognitive function. The population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) in the dentate gyrus area were recorded as a result of perforant pathway electrical stimulation. RESULTS Our study showed that Q10 and aerobic training alone ameliorate spatial memory in the acquisition phase, but have no effect on spatial memory in the retention phase. Q10 and exercise training synergistically promoted spatial memory in the retention phase. Q10 and exercise training separately and simultaneously mitigated cerebral ischemia-induced passive avoidance memory impairment in acquisition and retention phases. The EPSP did not differ between the groups, but exercise training and Q10 ameliorate the PS amplitude in hippocampal responses to perforant path stimulation. Exercising and Q10 simultaneously reduced the cerebral infarction volume. CONCLUSION Collectively, the findings of the present study imply that 12 weeks of aerobic training and Q10 supplementation alone can simultaneously reverse cerebral ischemia induced neurobehavioral deficits via amelioration of synaptic plasticity and a reduction in cerebral infarction volume in senescent rats.
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Affiliation(s)
- Kamal Ranjbar
- Department of Physical Education and Sport Science, Bandar Abbas Branch, Islamic Azad University, Bandar Abbas, Iran.
| | - Alireza Komaki
- Neurophysiology Research Center, Hamedan University of Medical Sciences, Hamedan, Iran
| | - Bayan Fayazi
- Department of Physical Education and Sport Science, Razi University, Kermanshah, Iran
| | - Ebrahim Zarrinkalam
- Department of Physical Education and Sport Science, Hamedan Branch, Islamic Azad University, Hamedan, Iran.
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Liu HG, Liu JJ, Wang YP, Wang HY, Sun A, Zhou Y, Cai MM, Qi MM. Impact of task-oriented training based on acupuncture rehabilitation on upper extremity function and quality of life of patients with early stroke. World J Clin Cases 2024; 12:3776-3784. [PMID: 38994303 PMCID: PMC11235430 DOI: 10.12998/wjcc.v12.i19.3776] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 05/05/2024] [Accepted: 05/07/2024] [Indexed: 06/29/2024] Open
Abstract
BACKGROUND Eighty percent of stroke patients develop upper limb dysfunction, especially hand dysfunction, which has a very slow recovery, resulting in economic burden to families and society. AIM To investigate the impact of task-oriented training based on acupuncture therapy on upper extremity function in patients with early stroke. METHODS Patients with early stroke hemiplegia who visited our hospital between January 2021 and October 2022 were divided into a control group and an observation group, each with 50 cases. The control group underwent head acupuncture plus routine upper limb rehabilitation training (acupuncture therapy). In addition to acupuncture and rehabilitation, the observation group underwent upper limb task-oriented training (30 min). Each group underwent treatment 5 d/wk for 4 wk. Upper extremity function was assessed in both groups using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Wolf Motor Function Rating Scale (WMFT), modified Barthel Index (MBI), and Canadian Occupational Performance Measure (COPM). Quality of life was evaluated using the Short-Form 36-Item Health Survey (SF-36). Clinical efficacy of the interventions was also evaluated. RESULTS Before intervention, no significant differences were observed in the FMA-UE, MBI, and WMFT scores between the two groups (P > 0.05). After intervention, the FMA-UE, WMFT, MBI, COPM-Functional Mobility and Satisfaction, and SF-36 scores increased in both groups (P < 0.05), with even higher scores in the observation group (P < 0.05). The observation group also obtained a higher total effective rate than the control group (P < 0.05). CONCLUSION Task-oriented training based on acupuncture rehabilitation significantly enhanced upper extremity mobility, quality of life, and clinical efficacy in patients with early stroke.
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Affiliation(s)
- Hong-Guang Liu
- Department of Rehabilitation Medicine, Ji Xi Ji Mine Hospital, Jixi 158100, Heilongjiang Province, China
| | - Jing-Jing Liu
- Department of Neurology, Ji Xi Ji Mine Hospital, Jixi 158100, Heilongjiang Province, China
| | - Yan-Ping Wang
- Department of Infectious Diseases, Jixi Hengshan District People's Hospital, Jixi 158100, Heilongjiang Province, China
| | - Hong-Ying Wang
- Department of Rehabilitation Medicine, Ji Xi Ji Mine Hospital, Jixi 158100, Heilongjiang Province, China
| | - Ao Sun
- Department of Rehabilitation Medicine, Ji Xi Ji Mine Hospital, Jixi 158100, Heilongjiang Province, China
| | - Yue Zhou
- Department of Rehabilitation Medicine, Ji Xi Ji Mine Hospital, Jixi 158100, Heilongjiang Province, China
| | - Ming-Ming Cai
- Department of Medical Care, Ji Xi Ji Mine Hospital, Jixi 158100, Heilongjiang Province, China
| | - Ming-Ming Qi
- Department of Science and Education, Ji Xi Ji Mine Hospital, Jixi 158100, Heilongjiang Province, China
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Wu X, Li C, Ke C, Huang C, Pan B, Wan C. The activation of AMPK/PGC-1α/GLUT4 signaling pathway through early exercise improves mitochondrial function and mitigates ischemic brain damage. Neuroreport 2024; 35:648-656. [PMID: 38813901 DOI: 10.1097/wnr.0000000000002048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
Mitochondria play a crucial role in maintaining cellular energy supply and serve as a source of energy for repairing nerve damage following a stroke. Given that exercise has the potential to enhance energy metabolism, investigating the impact of exercise on mitochondrial function provides a plausible mechanism for stroke treatment. In our study, we established the middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats and implemented early exercise intervention. Neurological severity scores, beam-walking test score, and weight were used to evaluate neurological function. The volume of cerebral infarction was measured by MRI. Nerve cell apoptosis was detected by TUNEL staining. Mitochondrial morphology and structure were detected by mitochondrial electron microscopy. Mitochondrial function was assessed using membrane potential and ATP measurements. Western blotting was used to detect the protein expression of AMPK/PGC-1α/GLUT4. Through the above experiments, we found that early exercise improved neurological function in rats after MCAO, reduced cerebral infarction volume and neuronal apoptosis, promoted the recovery of mitochondrial morphology and function. We further examined the protein expression of AMPK/PGC-1α/GLUT4 signaling pathway and confirmed that early exercise was able to increase its expression. Therefore, we suggest that early exercise initiated the AMPK/PGC-1α/GLUT4 signaling pathway, restoring mitochondrial function and augmenting energy supply. This, in turn, effectively improved both nerve and body function in rats following ischemic stroke.
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Affiliation(s)
- Xinyue Wu
- Department of Rehabilitation Medicine, Tianjin Medical University General Hospital
| | - Chen Li
- Department of Rehabilitation Medicine, Tianjin Medical University General Hospital
| | - Changkai Ke
- Department of Rehabilitation Medicine, Tianjin Medical University General Hospital
| | - Chuan Huang
- Department of Rehabilitation Medicine, Tianjin Medical University General Hospital
| | - Bingchen Pan
- Institute of Medical technology, Tianjin Medical University, Tianjin, China
| | - Chunxiao Wan
- Department of Rehabilitation Medicine, Tianjin Medical University General Hospital
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Jiang H, Kimura Y, Inoue S, Li C, Hatakeyama J, Wakayama M, Takamura D, Moriyama H. Effects of different exercise modes and intensities on cognitive performance, adult hippocampal neurogenesis, and synaptic plasticity in mice. Exp Brain Res 2024; 242:1709-1719. [PMID: 38806710 DOI: 10.1007/s00221-024-06854-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 05/14/2024] [Indexed: 05/30/2024]
Abstract
Exercise can induce beneficial improvements in cognition. However, the effects of different modes and intensities of exercise have yet to be explored in detail. This study aimed to identify the effects of different exercise modes (aerobic and resistance) and intensities (low and high) on cognitive performance, adult hippocampal neurogenesis and synaptic plasticity in mice. A total of 40 C57BL/6J mice were randomised into 5 groups (n = 8 mice per group): control, low-intensity aerobic exercise, high-intensity aerobic exercise, low-intensity resistance exercise, and high-intensity resistance exercise. The aerobic exercise groups underwent treadmill training, while the resistance exercise groups underwent ladder climbing training. At the end of the exercise period, cognitive performance was assessed by the Y-maze and Barnes maze. In addition, adult hippocampal neurogenesis was evaluated immunohistochemically by 5-bromo-2'-deoxyuridine (BrdU)/ neuronal nuclei (NeuN) co-labeling. The levels of synaptic plasticity-related proteins in the hippocampus, including synaptophysin (SYP) and postsynaptic density protein 95 (PSD-95), were analyzed by western blotting. Our results showed no significant differences in cognitive performance among the groups. However, high-intensity aerobic exercise significantly increased hippocampal adult neurogenesis relative to the control. A trend towards increased adult neurogenesis was observed in the low-intensity aerobic group compared to the control group. No significant changes in synaptic plasticity were observed among all groups. Our results indicate that high-intensity aerobic exercise may be the most potent stimulator of adult hippocampal neurogenesis.
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Affiliation(s)
- Hanlin Jiang
- Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan
| | - Yusuke Kimura
- Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan
| | - Shota Inoue
- Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan
| | - Changxin Li
- Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan
- Department of Rehabilitation, Affiliated Hospital of Zunyi Medical University, Zun Yi, China
| | - Junpei Hatakeyama
- Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan
| | - Masahiro Wakayama
- Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan
| | - Daisuke Takamura
- Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan
- Department of Rehabilitation, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Hideki Moriyama
- Life and Medical Sciences Area, Health Sciences Discipline, Kobe University, Tomogaoka 7-10-2, Suma-ku, Kobe, Hyogo, 654-0142, Japan.
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11
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Hong J, Chen J, Li C, Zhao F, Zhang J, Shan Y, Wen H. High-frequency rTMS alleviates cognitive impairment and regulates synaptic plasticity in the hippocampus of rats with cerebral ischemia. Behav Brain Res 2024; 467:115018. [PMID: 38678971 DOI: 10.1016/j.bbr.2024.115018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 04/15/2024] [Accepted: 04/24/2024] [Indexed: 05/01/2024]
Abstract
Poststroke cognitive impairment (PSCI) is a common complication of stroke, but effective treatments are currently lacking. Repetitive transcranial magnetic stimulation (rTMS) is gradually being applied to treat PSCI, but there is limited evidence of its efficacy. To determine rTMS effects on PSCI, we constructed a transient middle cerebral artery occlusion (tMCAO) rat model. Rats were then grouped by random digital table method: the sham group (n = 10), tMCAO group (n = 10) and rTMS group (n = 10). The shuttle box and Morris water maze (MWM) tests were conducted to detect the cognitive functions of the rats. In addition, synaptic density and synaptic ultrastructural parameters, including the active zone length, synaptic cleft width, and postsynaptic density (PSD) thickness, were quantified and analyzed using an electron microscope. What's more, synaptic associated proteins, including PSD95, SYN, and BDNF were detected by western blot. According to the shuttle box and MWM tests, rTMS improved tMCAO rats' cognitive functions, including spatial learning and memory and decision-making abilities. Electron microscopy revealed that rTMS significantly increased the synaptic density, synaptic active zone length and PSD thickness and decreased the synaptic cleft width. The western blot results showed that the expression of PSD95, SYN, and BDNF was markedly increased after rTMS stimulation. Based on these results, we propose that 20 Hz rTMS can significantly alleviate cognitive impairment after stroke. The underlying mechanism might be modulating the synaptic plasticity and up-regulating the expression PSD95, SYN, and BDNF in the hippocampus.
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Affiliation(s)
- Jiena Hong
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
| | - Jiemei Chen
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
| | - Chao Li
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
| | - Fei Zhao
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
| | - Jiantao Zhang
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
| | - Yilong Shan
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
| | - Hongmei Wen
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
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12
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Zhao H, Zhang T, Zhang H, Wang Y, Cheng L. Exercise-with-melatonin therapy improves sleep disorder and motor dysfunction in a rat model of ischemic stroke. Neural Regen Res 2024; 19:1336-1343. [PMID: 37905883 PMCID: PMC11467917 DOI: 10.4103/1673-5374.385844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 05/15/2023] [Accepted: 08/15/2023] [Indexed: 11/02/2023] Open
Abstract
Exercise-with-melatonin therapy has complementary and synergistic effects on spinal cord injury and Alzheimer’s disease, but its effect on stroke is still poorly understood. In this study, we established a rat model of ischemic stroke by occluding the middle cerebral artery for 60 minutes. We treated the rats with exercise and melatonin therapy for 7 consecutive days. Results showed that exercise-with-melatonin therapy significantly prolonged sleep duration in the model rats, increased delta power values, and regularized delta power rhythm. Additionally, exercise-with-melatonin therapy improved coordination, endurance, and grip strength, as well as learning and memory abilities. At the same time, it led to higher hippocampal CA1 neuron activity and postsynaptic density thickness and lower expression of glutamate receptor 2 than did exercise or melatonin therapy alone. These findings suggest that exercise-with-melatonin therapy can alleviate sleep disorder and motor dysfunction by increasing glutamate receptor 2 protein expression and regulating hippocampal CA1 synaptic plasticity.
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Affiliation(s)
- Haitao Zhao
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Department of Neurological Rehabilitation, Beijing Bo’ai Hospital, China Rehabilitation Research Center, Beijing, China
- School of Rehabilitation Medicine, University of Health and Rehabilitation Sciences, Qingdao, Shandong Province, China
- Laboratory of Brain Injury Repair and Rehabilitation, China Rehabilitation Science Institute, Beijing, China
| | - Tong Zhang
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Department of Neurological Rehabilitation, Beijing Bo’ai Hospital, China Rehabilitation Research Center, Beijing, China
- School of Rehabilitation Medicine, University of Health and Rehabilitation Sciences, Qingdao, Shandong Province, China
- Laboratory of Brain Injury Repair and Rehabilitation, China Rehabilitation Science Institute, Beijing, China
| | - Haojie Zhang
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Department of Neurological Rehabilitation, Beijing Bo’ai Hospital, China Rehabilitation Research Center, Beijing, China
- Laboratory of Brain Injury Repair and Rehabilitation, China Rehabilitation Science Institute, Beijing, China
| | - Yunlei Wang
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Department of Neurological Rehabilitation, Beijing Bo’ai Hospital, China Rehabilitation Research Center, Beijing, China
- Laboratory of Brain Injury Repair and Rehabilitation, China Rehabilitation Science Institute, Beijing, China
| | - Lingna Cheng
- School of Rehabilitation Medicine, Capital Medical University, Beijing, China
- Department of Neurological Rehabilitation, Beijing Bo’ai Hospital, China Rehabilitation Research Center, Beijing, China
- Laboratory of Brain Injury Repair and Rehabilitation, China Rehabilitation Science Institute, Beijing, China
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13
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Sadri I, Nikookheslat SD, Karimi P, Khani M, Nadimi S. Aerobic exercise training improves memory function through modulation of brain-derived neurotrophic factor and synaptic proteins in the hippocampus and prefrontal cortex of type 2 diabetic rats. J Diabetes Metab Disord 2024; 23:849-858. [PMID: 38932906 PMCID: PMC11196465 DOI: 10.1007/s40200-023-01360-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 11/23/2023] [Indexed: 06/28/2024]
Abstract
Aims/Introduction Defective insulin signaling in the brain may disrupt hippocampal neuroplasticity resulting in learning and memory impairments. Thus, this study investigated the effect of aerobic exercise training on cognitive function and synaptic protein markers in diabetic rats. Materials and methods Twenty male Wistar rats (200-250 g), were fed on high-fat diet and received a low dose of streptozotocin (35 mg/kg, i.p) to induce type 2 diabetes. Then diabetic animals were randomly divided into sedentary and training groups. The exercise training program was treadmill running at 27 m/min for 60 min/day for 8 weeks. One day after the last training session, Morris Water Maze (MWM) task was performed to evaluate spatial learning and memory. Then, the hippocamp and prefrontal cortex tissues were instantly dissected for immunoblotting assay of BDNF, GSK-3β, p-GSK-3β, P38, p-P38, ERK1/2, p-ERK1/2, heat shock protein-27 (HSP27), SNAP-25, synaptophysin, and PSD-95. Independent t-test analysis and two-way ANOVA was used to determine the differences under significance level of 0.05 using the 26th version of IBM SPSS statistical software. Results The results showed that aerobic exercise improved memory as assessed in the MWM task. Moreover, aerobic exercise up-regulated HSP27 and BDNF protein levels in the prefrontal cortex, and hippocampus coincided with robust elevations in SNAP25 and PSD-95 levels. Moreover, exercise reduced phosphorylated P38, while increased p-ERK1/2 and p-GSK-3β (p). Conclusion Our findings suggest that aerobic exercise may debilitate the harmful effects of diabetes on the cognitive function possibly through enhancing synaptic protein markers.
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Affiliation(s)
- Iraj Sadri
- Department of Physical Education and Sports Sciences, Islamic Azad University, Shabestar Branch, Shabestar, 5381637181 Iran
| | - Saeid Dabbagh Nikookheslat
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, 29 Bahman Blvd, Tabriz, 5166616471 Iran
| | - Pouran Karimi
- Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mostafa Khani
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, University of Tabriz, 29 Bahman Blvd, Tabriz, 5166616471 Iran
| | - Sanaz Nadimi
- Department of Chemistry and Biochemistry, Faculty of Science, University of Windsor, Windsor, ON Canada
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14
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Zhu W, Jia Q, Ferreira AC, Jiang H, Zhang J, Li B, Zhang M, Zhuo B, Lyu Y, Chen J, Li L, Tian G, Deng S, Meng Z, Shi X. Acupuncture for ischemic stroke: where are we now? ACUPUNCTURE AND HERBAL MEDICINE 2024; 4:36-55. [DOI: 10.1097/hm9.0000000000000094] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2025]
Abstract
Acupuncture is an effective treatment for ischemic stroke (IS) and plays a key role in neurological rehabilitation after IS. Acupuncture can improve the clinical symptoms of various complications after IS, including motor dysfunction, swallowing disorders, speech disorders, cognitive impairment, depression, insomnia, and fatigue. However, the mechanisms underlying the effects of acupuncture in IS remain unclear. Available evidence suggests that acupuncture may exert neuroprotective effects through neuroplasticity (neurogenesis and synaptogenesis), angiogenesis, cell proliferation and apoptosis, and regulation of oxidative stress, inflammation, and immunity. Further studies should be conducted to improve the high-quality evidence-based system of acupuncture intervention for IS, by focusing on the clinical and basic research design, increasing the sample size, standardizing and quantifying the standards of acupuncture operations, using multidisciplinary techniques and methods to systematically explore the key targets of acupuncture intervention for IS, and reveal the efficacy and mechanism of acupuncture in the treatment of IS.
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Affiliation(s)
- Weiming Zhu
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Qingqing Jia
- The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | | | - Hailun Jiang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Jieying Zhang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Boxuan Li
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Menglong Zhang
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Bifang Zhuo
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Yuanhao Lyu
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Junjie Chen
- Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Li Li
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Guang Tian
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Shizhe Deng
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Zhihong Meng
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Xuemin Shi
- First Teaching Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
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15
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Ebrahimi V, Rastegar-Moghaddam SH, Mohammadipour A. Therapeutic Potentials of MicroRNA-126 in Cerebral Ischemia. Mol Neurobiol 2023; 60:2062-2069. [PMID: 36596965 DOI: 10.1007/s12035-022-03197-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 12/23/2022] [Indexed: 01/05/2023]
Abstract
Stroke is a leading cause of death and disability worldwide. It is among the most common neurological disorders with an 8-10% lifetime risk. Ischemic stroke accounts for about 85% of all strokes and damages the brain tissue via various damaging mechanisms. Following cerebral ischemia, the disrupted blood-brain barrier (BBB) leads to cerebral edema formation caused by activation of oxidative stress, inflammation, and apoptosis, targeting primarily endothelial cells. Activation of the protective mechanisms might favor fewer damages to the neural tissue. MicroRNA (miR)-126 is an endothelial cell-specific miR involved in angiogenesis. MiR-126 orchestrates endothelial progenitor cell functions under hypoxic conditions and could inhibit ischemia-induced oxidative stress and inflammation. It alleviates the BBB disruption by preventing an augment in matrix metalloproteinase level and halting the decrease in the junctional proteins, including zonula occludens-1 (ZO-1), claudin-5, and occludin levels. Moreover, miR-126 enhances post-stroke angiogenesis and neurogenesis. This work provides a therapeutic perspective for miR-126 as a new approach to treating cerebral ischemia.
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Affiliation(s)
- Vahid Ebrahimi
- Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Abbas Mohammadipour
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. .,Applied Biomedical Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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16
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Chi X, Wang L, Liu H, Zhang Y, Shen W. Post-stroke cognitive impairment and synaptic plasticity: A review about the mechanisms and Chinese herbal drugs strategies. Front Neurosci 2023; 17:1123817. [PMID: 36937659 PMCID: PMC10014821 DOI: 10.3389/fnins.2023.1123817] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 02/13/2023] [Indexed: 03/06/2023] Open
Abstract
Post-stroke cognitive impairment, is a major complication of stroke, characterized by cognitive dysfunction, which directly affects the quality of life. Post-stroke cognitive impairment highlights the causal relationship between stroke and cognitive impairment. The pathological damage of stroke, including the increased release of excitatory amino acids, oxidative stress, inflammatory responses, apoptosis, changed neurotrophic factor levels and gene expression, influence synaptic plasticity. Synaptic plasticity refers to the activity-dependent changes in the strength of synaptic connections and efficiency of synaptic transmission at pre-existing synapses and can be divided into structural synaptic plasticity and functional synaptic plasticity. Changes in synaptic plasticity have been proven to play important roles in the occurrence and treatment of post-stroke cognitive impairment. Evidence has indicated that Chinese herbal drugs have effect of treating post-stroke cognitive impairment. In this review, we overview the influence of pathological damage of stroke on synaptic plasticity, analyze the changes of synaptic plasticity in post-stroke cognitive impairment, and summarize the commonly used Chinese herbal drugs whose active ingredient or extracts can regulate synaptic plasticity. This review will summarize the relationship between post-stroke cognitive impairment and synaptic plasticity, provide new ideas for future exploration of the mechanism of post-stroke cognitive impairment, compile evidence of applying Chinese herbal drugs to treat post-stroke cognitive impairment and lay a foundation for the development of novel formulas for treating post-stroke cognitive impairment.
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Affiliation(s)
- Xiansu Chi
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Liuding Wang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hongxi Liu
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Yunling Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wei Shen
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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17
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Post-Stroke Environmental Enrichment Improves Neurogenesis and Cognitive Function and Reduces the Generation of Aberrant Neurons in the Mouse Hippocampus. Cells 2023; 12:cells12040652. [PMID: 36831319 PMCID: PMC9954243 DOI: 10.3390/cells12040652] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/08/2023] [Accepted: 02/09/2023] [Indexed: 02/22/2023] Open
Abstract
Ischemic lesions stimulate adult neurogenesis in the dentate gyrus, however, this is not associated with better cognitive function. Furthermore, increased neurogenesis is associated with the formation of aberrant neurons. In a previous study, we showed that a running task after a stroke not only increases neurogenesis but also the number of aberrant neurons without improving general performance. Here, we determined whether stimulation in an enriched environment after a lesion could increase neurogenesis and cognitive function without enhancing the number of aberrant neurons. After an ischemic stroke induced by MCAO, animals were transferred to an enriched environment containing a running wheel, tunnels and nest materials. A GFP-retroviral vector was delivered on day 3 post-stroke and a modified water maze test was performed 6 weeks after the lesion. We found that the enriched environment significantly increased the number of new neurons compared with the unstimulated stroke group but not the number of aberrant cells after a lesion. Increased neurogenesis after environmental enrichment was associated with improved cognitive function. Our study showed that early placement in an enriched environment after a stroke lesion markedly increased neurogenesis and flexible learning but not the formation of aberrant neurons, indicating that rehabilitative training, as a combination of running wheel training and enriched environment housing, improved functional and structural outcomes after a stroke.
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18
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Wu C, Yang J, Ding R, Li X, Yang Z, Zhu M, Liu Z. Identification of a costimulatory molecule-based signature to predict prognostic risk of pancreatic adenocarcinoma. ALL LIFE 2022. [DOI: 10.1080/26895293.2022.2090450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
Affiliation(s)
- Chao Wu
- Department of Oncology, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Jingyue Yang
- Department of Oncology, Xijing Hospital, Air Force Military Medical University, Xi’an, People’s Republic of China
| | - Rui Ding
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, People’s Republic of China
| | - Xiao Li
- Department of Hepatobiliary Surgery, Xijing Hospital, Air Force Military Medical University, Xi’an, People’s Republic of China
| | - Zhi Yang
- The IVD Medical Marketing Department, 3D Medicines Inc., Shanghai, People’s Republic of China
| | - Min Zhu
- Department of Oncology, The Fifth medical center, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Zhengcai Liu
- Department of Hepatopancreatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China
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19
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Ulanov M, Shtyrov Y. Oscillatory beta/alpha band modulations: A potential biomarker of functional language and motor recovery in chronic stroke? Front Hum Neurosci 2022; 16:940845. [PMID: 36226263 PMCID: PMC9549964 DOI: 10.3389/fnhum.2022.940845] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/19/2022] [Indexed: 11/13/2022] Open
Abstract
Stroke remains one of the leading causes of various disabilities, including debilitating motor and language impairments. Though various treatments exist, post-stroke impairments frequently become chronic, dramatically reducing daily life quality, and requiring specific rehabilitation. A critical goal of chronic stroke rehabilitation is to induce, usually through behavioral training, experience-dependent plasticity processes in order to promote functional recovery. However, the efficiency of such interventions is typically modest, and very little is known regarding the neural dynamics underpinning recovery processes and possible biomarkers of their efficiency. Some studies have emphasized specific alterations of excitatory–inhibitory balance within distributed neural networks as an important recovery correlate. Neural processes sensitive to these alterations, such as task-dependent oscillatory activity in beta as well as alpha bands, may be candidate biomarkers of chronic stroke functional recovery. In this review, we discuss the results of studies on motor and language recovery with a focus on oscillatory processes centered around the beta band and their modulations during functional recovery in chronic stroke. The discussion is based on a framework where task-dependent modulations of beta and alpha oscillatory activity, generated by the deep cortical excitatory–inhibitory microcircuits, serve as a neural mechanism of domain-general top-down control processes. We discuss the findings, their limitations, and possible directions for future research.
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Affiliation(s)
- Maxim Ulanov
- Centre for Cognition and Decision Making, Institute for Cognitive Neuroscience, HSE University, Moscow, Russia
- *Correspondence: Maxim Ulanov,
| | - Yury Shtyrov
- Center of Functionally Integrative Neuroscience (CFIN), Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
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20
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Poststroke Cognitive Impairment Research Progress on Application of Brain-Computer Interface. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9935192. [PMID: 35252458 PMCID: PMC8896931 DOI: 10.1155/2022/9935192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 12/20/2021] [Accepted: 12/23/2021] [Indexed: 12/19/2022]
Abstract
Brain-computer interfaces (BCIs), a new type of rehabilitation technology, pick up nerve cell signals, identify and classify their activities, and convert them into computer-recognized instructions. This technique has been widely used in the rehabilitation of stroke patients in recent years and appears to promote motor function recovery after stroke. At present, the application of BCI in poststroke cognitive impairment is increasing, which is a common complication that also affects the rehabilitation process. This paper reviews the promise and potential drawbacks of using BCI to treat poststroke cognitive impairment, providing a solid theoretical basis for the application of BCI in this area.
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21
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Dehqanizadeh B, Mohammadi ZF, Kalani AHT, Mirghani SJ. Effect of Early Exercise on Inflammatory Parameters and Apoptosis in CA1 Area of the Hippocampus Following Cerebral Ischemia-reperfusion in Rats. Brain Res Bull 2022; 182:102-110. [DOI: 10.1016/j.brainresbull.2022.02.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 12/28/2022]
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22
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Borisova VA, Isakova EV, Kotov SV. [Possibilities of the brain-computer interface in the correction of post-stroke cognitive impairments]. Zh Nevrol Psikhiatr Im S S Korsakova 2022; 122:60-66. [PMID: 36582163 DOI: 10.17116/jnevro202212212260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
In recent years, brain-computer interfaces have been widely used in neurorehabilitation, and an extensive database of results from clinical studies conducted around the world has been accumulated, demonstrating their effectiveness in restoring motor function after a stroke. Currently, their use in post-stroke cognitive impairment is expanding. This article discusses the potential and prospects for using brain-computer interfaces for the treatment of cognitive disorders, reviews the experience of using it, presents the results of clinical studies in stroke patients, evaluates the possibilities of using this technology, describes the prospects, new directions of work on studying its effects.
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Affiliation(s)
- V A Borisova
- Vladimirskii Moscow Regional Research Clinical Institute, Moscow, Russia
| | - E V Isakova
- Vladimirskii Moscow Regional Research Clinical Institute, Moscow, Russia
| | - S V Kotov
- Vladimirskii Moscow Regional Research Clinical Institute, Moscow, Russia
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23
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Var SR, Shetty AV, Grande AW, Low WC, Cheeran MC. Microglia and Macrophages in Neuroprotection, Neurogenesis, and Emerging Therapies for Stroke. Cells 2021; 10:3555. [PMID: 34944064 PMCID: PMC8700390 DOI: 10.3390/cells10123555] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 12/12/2021] [Accepted: 12/15/2021] [Indexed: 12/20/2022] Open
Abstract
Stroke remains the number one cause of morbidity in the United States. Within weeks to months after an ischemic event, there is a resolution of inflammation and evidence of neurogenesis; however, years following a stroke, there is evidence of chronic inflammation in the central nervous system, possibly by the persistence of an autoimmune response to brain antigens as a result of ischemia. The mechanisms underlying the involvement of macrophage and microglial activation after stroke are widely acknowledged as having a role in ischemic stroke pathology; thus, modulating inflammation and neurological recovery is a hopeful strategy for treating the long-term outcomes after ischemic injury. Current treatments fail to provide neuroprotective or neurorestorative benefits after stroke; therefore, to ameliorate brain injury-induced deficits, therapies must alter both the initial response to injury and the subsequent inflammatory process. This review will address differences in macrophage and microglia nomenclature and summarize recent work in elucidating the mechanisms of macrophage and microglial participation in antigen presentation, neuroprotection, angiogenesis, neurogenesis, synaptic remodeling, and immune modulating strategies for treating the long-term outcomes after ischemic injury.
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Affiliation(s)
- Susanna R. Var
- Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA; (S.R.V.); (A.W.G.)
- Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN 55108, USA
- Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA;
| | - Anala V. Shetty
- Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA;
- Department of Biological Sciences, University of Minnesota Medical School, Minneapolis, MN 55108, USA
| | - Andrew W. Grande
- Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA; (S.R.V.); (A.W.G.)
- Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA;
| | - Walter C. Low
- Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA; (S.R.V.); (A.W.G.)
- Stem Cell Institute, University of Minnesota Medical School, Minneapolis, MN 55455, USA;
| | - Maxim C. Cheeran
- Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN 55108, USA
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Li C, Ke C, Su Y, Wan C. Exercise Intervention Promotes the Growth of Synapses and Regulates Neuroplasticity in Rats With Ischemic Stroke Through Exosomes. Front Neurol 2021; 12:752595. [PMID: 34777222 PMCID: PMC8581302 DOI: 10.3389/fneur.2021.752595] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 09/27/2021] [Indexed: 12/17/2022] Open
Abstract
Background: Stroke is the leading cause of death and disability. Exercise produces neuroprotection by improving neuroplasticity. Exercise can induce exosome production. According to several studies, exosomes are involved in repairing brain function, but the relationship and mechanism of exercise, exosomes, and neuroprotection have not been elucidated. This study intends to explore the relationship and potential mechanism by observing the changes in the exosome level, infarct volume, neurological function and behavioral scores, synapses, and corticospinal tract (CST). Methods: Rats were randomly divided into four groups: a sham operation (SHAM) group, middle cerebral artery occlusion (MCAO) with sedentary intervention (SED-MCAO) group, MCAO with exercise intervention (EX-MCAO) group, and MCAO with exercise intervention and exosome injection (EX-MCAO-EXO) group. The exercise intervention was started 1 day after MCAO and lasted for 4 weeks. All rats were assessed using the modified neurological severity score (mNSS). The levels of exosomes in serum and brain, gait analysis, and magnetic resonance scan were performed 1 and 4 weeks after the intervention. After 4 weeks of intervention, the number of synapses, synaptophysin (Syn), and postsynaptic density protein 95(PSD-95) expression was detected. Results: After 4 weeks of intervention, (1) the EX-MCAO and EX-MCAO-EXO groups showed higher serum exosome (pEX−MCAO = 0.000, pEX−MCAO−EXO = 0.000) and brain exosome (pEX−MCAO = 0.001, pEX−MCAO−EXO = 0.000) levels than the SED-MCAO group, of which the EX-MCAO group had the highest serum exosome (p = 0.000) and the EX-MCAO-EXO group had the highest brain exosome (p = 0.03) levels. (2) The number of synapses in the EX-MCAO (p = 0.032) and EX-MCAO-EXO groups (p = 0.000) was significantly higher than that in the SED-MCAO group. The EX-MCAO-EXO group exhibited a greater number of synapses than the EX-MCAO (p = 0.000) group. (3) The synaptic plasticity-associated proteins were expressed significantly higher in the EX-MCAO (pSyn = 0.010, pPSD−95 = 0.044) and EX-MCAO-EXO (pSyn = 0.000, pPSD−95 = 0.000) groups than in the SED-MCAO group, and the EX-MCAO-EXO group (pSyn = 0.000, pPSD−95 = 0.046) had the highest expression. (4) Compared with the SED-MCAO group, the EX-MCAO group had significantly improved infarct volume ratio (p = 0.000), rFA value (p = 0.000), and rADC (p = 0.000). Compared with the EX-MCAO group, the EX-MCAO-EXO group had a significantly improved infarct volume ratio (p = 0.000), rFA value (p = 0.000), and rADC value (p = 0.001). (5) Compared with the SED-MCAO group, the EX-MCAO group (p = 0.001) and EX-MCAO-EXO group (p = 0.000) had significantly lower mNSS scores and improved gait. (6) The brain exosome levels were negatively correlated with the mNSS score, infarct volume ratio, and rADC value and positively correlated with the rFA value, Syn, and PSD-95 expression. The serum and brain exosome levels showed a positive correlation. Conclusions: Exercise intervention increases the serum exosome level in MCAO rats, which are recruited into the brain, leading to improved synaptic growth and CST integrity, a reduced infarct volume, and improved neurological function and gait.
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Affiliation(s)
- Chen Li
- Department of Physical Medicine and Rehabilitation, Tianjin Medical University General Hospital, Tianjin, China
| | - Changkai Ke
- Department of Physical Medicine and Rehabilitation, Tianjin Medical University General Hospital, Tianjin, China
| | - Yue Su
- Department of Physical Medicine and Rehabilitation, Tianjin Medical University General Hospital, Tianjin, China
| | - Chunxiao Wan
- Department of Physical Medicine and Rehabilitation, Tianjin Medical University General Hospital, Tianjin, China
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25
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Zhang L, Wei W, Ai X, Kilic E, Hermann DM, Venkataramani V, Bähr M, Doeppner TR. Extracellular vesicles from hypoxia-preconditioned microglia promote angiogenesis and repress apoptosis in stroke mice via the TGF-β/Smad2/3 pathway. Cell Death Dis 2021; 12:1068. [PMID: 34753919 PMCID: PMC8578653 DOI: 10.1038/s41419-021-04363-7] [Citation(s) in RCA: 93] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 09/15/2021] [Accepted: 10/20/2021] [Indexed: 12/17/2022]
Abstract
Systemic transplantation of oxygen-glucose deprivation (OGD)-preconditioned primary microglia enhances neurological recovery in rodent stroke models, albeit the underlying mechanisms have not been sufficiently addressed. Herein, we analyzed whether or not extracellular vesicles (EVs) derived from such microglia are the biological mediators of these observations and which signaling pathways are involved in the process. Exposing bEnd.3 endothelial cells (ECs) and primary cortical neurons to OGD, the impact of EVs from OGD-preconditioned microglia on angiogenesis and neuronal apoptosis by the tube formation assay and TUNEL staining was assessed. Under these conditions, EV treatment stimulated both angiogenesis and tube formation in ECs and repressed neuronal cell injury. Characterizing microglia EVs by means of Western blot analysis and other techniques revealed these EVs to be rich in TGF-β1. The latter turned out to be a key compound for the therapeutic potential of microglia EVs, affecting the Smad2/3 pathway in both ECs and neurons. EV infusion in stroke mice confirmed the aforementioned in vitro results, demonstrating an activation of the TGF-β/Smad2/3 signaling pathway within the ischemic brain. Furthermore, enriched TGF-β1 in EVs secreted from OGD-preconditioned microglia stimulated M2 polarization of residing microglia within the ischemic cerebral environment, which may contribute to a regulation of an early inflammatory response in postischemic hemispheres. These observations are not only interesting from the mechanistic point of view but have an immediate therapeutic implication as well, since stroke mice treated with such EVs displayed a better functional recovery in the behavioral test analyses. Hence, the present findings suggest a new way of action of EVs derived from OGD-preconditioned microglia by regulating the TGF-β/Smad2/3 pathway in order to promote tissue regeneration and neurological recovery in stroke mice.
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Affiliation(s)
- Lin Zhang
- Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
| | - Wei Wei
- Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
| | - Xiaoyu Ai
- Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
| | - Ertugrul Kilic
- Regenerative and Restorative Medical Research Center, Istanbul Medipol University, Istanbul, Turkey
| | - Dirk M Hermann
- Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Vivek Venkataramani
- Department of Medicine II, University Hospital Frankfurt, Frankfurt, Germany
- Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
| | - Mathias Bähr
- Department of Neurology, University Medical Center Göttingen, Göttingen, Germany
| | - Thorsten R Doeppner
- Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
- Regenerative and Restorative Medical Research Center, Istanbul Medipol University, Istanbul, Turkey.
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26
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Zhu L, Fan JH, Chao FL, Zhou CN, Jiang L, Zhang Y, Luo YM, Zhang L, Xiao Q, Yang H, Zhang SS, Wu H, Tang Y. Running exercise protects spinophilin-immunoreactive puncta and neurons in the medial prefrontal cortex of APP/PS1 transgenic mice. J Comp Neurol 2021; 530:858-870. [PMID: 34585379 DOI: 10.1002/cne.25252] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/15/2021] [Accepted: 09/17/2021] [Indexed: 11/06/2022]
Abstract
The medial prefrontal cortex (mPFC) is thought to be closely associated with emotional processes, decision making, and memory. Previous studies have identified the prefrontal cortex as one of the most vulnerable brain regions in Alzheimer's disease (AD). Running exercise has widely been recognized as a simple and effective method of physical activity that enhances brain function and slows the progression of AD. However, the effect of exercise on the mPFC of AD is unclear. To address these issues, we investigated the effects of 4 months of exercise on the numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of 12-month-old APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice using stereological methods. The spatial learning and memory abilities of mice were tested using the Morris water maze. Four months of running exercise delayed declines in spatial learning and memory abilities. The stereological results showed significantly lower numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of APP/PS1 mice than in the wild-type control group. The numbers of spinophilin-immunoreactive puncta and neurons in the mPFC of running APP/PS1 mice were significantly greater than those in the APP/PS1 control mice. In addition, running-induced improvements in spatial learning and memory were significantly associated with running-induced increases in spinophilin-immunoreactive puncta and neurons numbers in the mPFC. Running exercise could delay the loss of spinophilin-immunoreactive puncta and neurons in the mPFC of APP/PS1 mice. This finding might provide an important structural basis for exercise-induced improvements in the spatial learning and memory abilities of individuals with AD.
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Affiliation(s)
- Lin Zhu
- Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, P. R. China.,Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China
| | - Jin-Hua Fan
- School of Life Sciences, Southwest University, Chongqing, P. R. China
| | - Feng-Lei Chao
- Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, P. R. China.,Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China
| | - Chun-Ni Zhou
- Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, P. R. China.,Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China
| | - Lin Jiang
- Lab Teaching & Management Center, Chongqing Medical University, Chongqing, P. R. China
| | - Yi Zhang
- Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China
| | - Yan-Min Luo
- Department of Physiology, Chongqing Medical University, Chongqing, P. R. China
| | - Lei Zhang
- Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, P. R. China.,Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China
| | - Qian Xiao
- Department of Radioactive Medicine, Chongqing Medical University, Chongqing, P. R. China
| | - Hao Yang
- Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, P. R. China.,Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China
| | - Shan-Shan Zhang
- Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, P. R. China.,Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China
| | - Hong Wu
- Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, P. R. China.,Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China
| | - Yong Tang
- Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, P. R. China.,Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P. R. China
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27
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Yu F, Huang T, Ran Y, Li D, Ye L, Tian G, Xi J, Liu Z. New Insights Into the Roles of Microglial Regulation in Brain Plasticity-Dependent Stroke Recovery. Front Cell Neurosci 2021; 15:727899. [PMID: 34421544 PMCID: PMC8374071 DOI: 10.3389/fncel.2021.727899] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 07/13/2021] [Indexed: 01/07/2023] Open
Abstract
Stroke remains the leading cause of long-term disability worldwide with significant long-term sequelae. However, there is no highly effective treatment to enhance post-stroke recovery despite extensive efforts in exploring rehabilitative therapies. Neurorehabilitation is recognized as the cornerstone of functional restoration therapy in stroke, where treatments are focused on neuroplastic regulation to reverse neural structural disruption and improve neurofunctional networks. Post-stroke neuroplasticity changes begin within hours of symptom onset and reaches a plateau by 3 to 4 weeks within the global brain in animal studies. It plays a determining role in spontaneous stroke recovery. Microglia are immediately activated following cerebral ischemia, which has been found both proximal to the primary ischemic injury and at the remote brain regions which have functional connections to the primary injury area. Microglia exhibit different activation profiles based on the microenvironment and adaptively switch their phenotypes in a spatiotemporal manner in response to brain injuries. Microglial activation coincides with neuroplasticity after stroke, which provides the fundamental base for the microglia-mediated inflammatory responses involved in the entire neural network rewiring and brain repair. Microglial activation exerts important effects on spontaneous recovery after stroke, including structural and functional reestablishment of neurovascular networks, neurogenesis, axonal remodeling, and blood vessel regeneration. In this review, we focus on the crosstalk between microglial activation and endogenous neuroplasticity, with a special focus on the plastic alterations in the whole brain network and their implications for structural and functional restoration after stroke. We then summarize recent advances in the impacts of microglial phenotype polarization on brain plasticity, trying to discuss the potential efficacy of microglia-based extrinsic restorative interventions in promoting post-stroke recovery.
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Affiliation(s)
- Fang Yu
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States.,Department of Anesthesiology, Westchester Medical Center, New York Medical College, Valhalla, NY, United States
| | - Tingting Huang
- Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuanyuan Ran
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Da Li
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Lin Ye
- School of Materials Science and Engineering, Beijing Institute of Technology, Beijing, China
| | - Guiqin Tian
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Jianing Xi
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
| | - Zongjian Liu
- Department of Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China
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28
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Sui YF, Tong LQ, Zhang XY, Song ZH, Guo TC. Effects of paired associated stimulation with different stimulation position on motor cortex excitability and upper limb motor function in patients with cerebral infarction. J Clin Neurosci 2021; 90:363-369. [PMID: 34275577 DOI: 10.1016/j.jocn.2021.06.028] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE To investigate the effects of paired associated stimulation (PAS) with different stimulation position on motor cortex excitability and upper limb motor function in patients with cerebral infarction. METHOD A total of 120 volunteers with cerebral infarction were randomly divided into four groups. Based on conventional rehabilitation treatment, the PAS stimulation group was given the corresponding position of PAS treatment once a day for 28 consecutive days. The MEP amplitude and RMT of both hemispheres were assessed before and after treatment, and a simple upper limb Function Examination Scale (STEF) score, simplified upper limb Fugl-Meyer score (FMA), and improved Barthel Index (MBI) were used to assess upper limb motor function in the four groups. RESULTS Following PAS, the MEP amplitude decreased, and the RMT of abductor pollicis brevis (APB) increased on the contralesional side, while the MEP amplitude increased and the RMT of APB decreased on the ipsilesional side. After 28 consecutive days the scores of STEF, FMA, and MBI in the bilateral stimulation group were significantly better than those in the ipsilesional stimulation group and the contralesional stimulation group, but there was no significant difference in the scores of STEF, FMA, and MBI between the ipsilesional stimulation group and the contralesional stimulation group. CONCLUSION The excitability of the motor cortex can be changed when the contralesional side or the ipsilesional side was given the corresponding PAS stimulation, while the bilateral PAS stimulation can more easily cause a change of excitability of the motor cortex, resulting in better recovery of the upper limb function.
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Affiliation(s)
- Yan-Fang Sui
- Department of Rehabilitation Medicine, The Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou 570208, China
| | - Liang-Qian Tong
- Department of Rehabilitation Medicine, The Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou 570208, China
| | - Xiang-Yu Zhang
- Department of Rehabilitation Medicine, The 5th Hospital of Zhengzhou University, Zhengzhou 470000, China
| | - Zhen-Hua Song
- Department of Rehabilitation Medicine, The Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou 570208, China.
| | - Tie-Cheng Guo
- Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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29
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Zheng Y, Yan C, Shi H, Niu Q, Liu Q, Lu S, Zhang X, Cheng Y, Teng M, Wang L, Zhang X, Hu X, Li J, Lu X, Reinhardt JD. Time Window for Ischemic Stroke First Mobilization Effectiveness: Protocol for an Investigator-Initiated Prospective Multicenter Randomized 3-Arm Clinical Trial. Phys Ther 2021; 101:6123582. [PMID: 33513232 DOI: 10.1093/ptj/pzab038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 10/01/2020] [Accepted: 01/02/2021] [Indexed: 11/13/2022]
Abstract
OBJECTIVE The purpose of this study is to investigate the optimal time window for initiating mobilizing after acute ischemic stroke. METHODS The TIME Trial is a pragmatic, investigator-initiated, multi-center, randomized, 3-arm parallel group, clinical trial. This trial will be conducted in 57 general hospitals in mainland China affiliated with the China Stroke Databank Center and will enroll 6033 eligible patients with acute ischemic stroke. Participants will be randomly allocated to either (1) the very early mobilization group in which mobilization is initiated within 24 hours from stroke onset, (2) the early mobilization group in which mobilization begins between 24 and 72 hours poststroke, or (3) the late mobilization group in which mobilization is started after 72 hours poststroke. The mobilization protocol is otherwise standardized and identical for each comparison group. Mobilization is titrated by baseline mobility level and progress of patients throughout the intervention period. The primary outcome is death or disability assessed with the modified Rankin scale at 3 months poststroke. Secondary outcomes include impairment score of the National Institutes of Health Stroke Scale, dependence in activities of daily living as measured using the modified Barthel Index, cognitive ability assessed with the Mini-Mental State Examination, incidence of adverse events, hospital length of stay, and total medical costs. IMPACT The TIME Trial is designed to answer the question "when is the best time to start mobilization after stroke?" The effect of timing is isolated from the effect of type and dose of mobilization by otherwise applying a standard mobilization protocol across groups. The TIME Trial may, therefore, contribute to increasing the knowledge base regarding the optimal time window for initiating mobilization after acute ischemic stroke.
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Affiliation(s)
- Yu Zheng
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chengjie Yan
- Department of Neurorehabilitation, Kunshan Rehabilitation Hospital, Kunshan, China
| | - Haibin Shi
- Department of Interventional Radiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qi Niu
- Department of Geriatric Neurology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qianghui Liu
- Department of Emergency, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shanshan Lu
- Department of Nuclear Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xintong Zhang
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yihui Cheng
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Meiling Teng
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lu Wang
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiu Zhang
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaorong Hu
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian Li
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiao Lu
- Department of Rehabilitation Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jan D Reinhardt
- Institute for Disaster Management and Reconstruction of Sichuan University, Chengdu, China.,Hong Kong Polytechnic University, Chengdu, China.,Swiss Paraplegic Research, Nottwil, Switzerland.,Department of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland
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30
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Environmental Enrichment Enhances Ca v 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic-Ischemic Encephalopathy. Int J Mol Sci 2021; 22:ijms22073414. [PMID: 33810296 PMCID: PMC8037860 DOI: 10.3390/ijms22073414] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 03/23/2021] [Indexed: 12/16/2022] Open
Abstract
Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O2 hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Cav 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Cav 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Cav 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.
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31
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Hong J, Chen J, Li C, An D, Tang Z, Wen H. High-Frequency rTMS Improves Cognitive Function by Regulating Synaptic Plasticity in Cerebral Ischemic Rats. Neurochem Res 2021; 46:276-286. [PMID: 33136229 DOI: 10.1007/s11064-020-03161-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 10/22/2020] [Accepted: 10/26/2020] [Indexed: 01/07/2023]
Abstract
Poststroke cognitive impairment (PSCI) is one of the most severe sequelae of stroke and lacks effective treatment. Previous studies have shown that high-frequency repetitive transcranial magnetic stimulation (rTMS) may be a promising PSCI therapeutic approach, but the underlying mechanism is unclear. To uncover the effect of rTMS on PSCI, a transient middle cerebral artery occlusion (tMCAO) model was established. Modified Neurological Severity Score (mNSS) test and Morris Water Maze (MWM) test were performed to assess the neurological and cognitive function of rats. Furthermore, to explore the underlying mechanism, differentially expressed genes (DEGs) in the hippocampus of rats in the rTMS group and tMCAO group were compared using RNA sequencing. Then, bioinformatics analysis, including gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis, was conducted to elaborate these DEGs. Our results indicated that high-frequency rTMS could significantly improve neurological and cognitive function, according to mNSS and MWM tests. We found 85 DEGs, including 71 upregulated genes and 14 downregulated genes, between the rTMS group and tMCAO group. The major functional category was related to chemical synaptic transmission modulation and several DEGs were significantly upregulated in processes related to synaptic plasticity, such as glutamatergic synapses. Calb2, Zic1, Kcnk9, and Grin3a were notable in PPI analysis. These results demonstrate that rTMS has a beneficial effect on PSCI, and its mechanism may be related to the regulation of synaptic plasticity and functional genes such as Calb2, Zic1, Kcnk9, and Grin3a in the hippocampus.
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Affiliation(s)
- Jiena Hong
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China
| | - Jiemei Chen
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China
| | - Chao Li
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China
| | - Delian An
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China
| | - Zhiming Tang
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China
| | - Hongmei Wen
- Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
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32
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Hu J, Liu PL, Hua Y, Gao BY, Wang YY, Bai YL, Chen C. Constraint-induced movement therapy enhances AMPA receptor-dependent synaptic plasticity in the ipsilateral hemisphere following ischemic stroke. Neural Regen Res 2021; 16:319-324. [PMID: 32859791 PMCID: PMC7896237 DOI: 10.4103/1673-5374.290900] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
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.
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Affiliation(s)
- Jian Hu
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Pei-Le Liu
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yan Hua
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Bei-Yao Gao
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yu-Yuan Wang
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yu-Long Bai
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Chan Chen
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Quarta E, Cohen EJ, Bravi R, Minciacchi D. Future Portrait of the Athletic Brain: Mechanistic Understanding of Human Sport Performance Via Animal Neurophysiology of Motor Behavior. Front Syst Neurosci 2020; 14:596200. [PMID: 33281568 PMCID: PMC7705174 DOI: 10.3389/fnsys.2020.596200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 10/19/2020] [Indexed: 11/24/2022] Open
Abstract
Sport performances are often showcases of skilled motor control. Efforts to understand the neural processes subserving such movements may teach us about general principles of behavior, similarly to how studies on neurological patients have guided early work in cognitive neuroscience. While investigations on non-human animal models offer valuable information on the neural dynamics of skilled motor control that is still difficult to obtain from humans, sport sciences have paid relatively little attention to these mechanisms. Similarly, knowledge emerging from the study of sport performance could inspire innovative experiments in animal neurophysiology, but the latter has been only partially applied. Here, we advocate that fostering interactions between these two seemingly distant fields, i.e., animal neurophysiology and sport sciences, may lead to mutual benefits. For instance, recording and manipulating the activity from neurons of behaving animals offer a unique viewpoint on the computations for motor control, with potentially untapped relevance for motor skills development in athletes. To stimulate such transdisciplinary dialog, in the present article, we also discuss steps for the reverse translation of sport sciences findings to animal models and the evaluation of comparability between animal models of a given sport and athletes. In the final section of the article, we envision that some approaches developed for animal neurophysiology could translate to sport sciences anytime soon (e.g., advanced tracking methods) or in the future (e.g., novel brain stimulation techniques) and could be used to monitor and manipulate motor skills, with implications for human performance extending well beyond sport.
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Affiliation(s)
| | | | | | - Diego Minciacchi
- Physiological Sciences Section, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Yang K, Zhou Y, Zhou L, Yan F, Guan L, Liu H, Liu W. Synaptic Plasticity After Focal Cerebral Ischemia Was Attenuated by Gap26 but Enhanced by GAP-134. Front Neurol 2020; 11:888. [PMID: 32982919 PMCID: PMC7479336 DOI: 10.3389/fneur.2020.00888] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 07/13/2020] [Indexed: 12/15/2022] Open
Abstract
Objective: Synaptic plasticity is critical for neurorehabilitation after focal cerebral ischemia. Connexin 43 (Cx43), the main component of the gap junction, has been shown to be pivotal for synaptic plasticity. The objective of this study was to investigate the role of the Cx43 inhibitor (Gap26) and gap junction modifier (GAP-134) in neurorehabilitation and to study their contribution to synaptic plasticity after focal ischemia. Methods: Time course expression of both total and phosphorylated Cx43 (p-Cx43) were detected by western blotting at 3, 7, and 14 d after focal ischemia. Gap26 and GAP-134 were administered starting from 3 d post focal ischemia. Neurological performances were evaluated by balance beam walking test and Y-maze test at 1, 3, and 7 d. Golgi staining and transmission electron microscope (TEM) detection were conducted at 7 d for observing dendritic spine numbers and synaptic ultrastructure, respectively. Immunofluorescent staining was used at 7 d for detection of synaptic plasticity markers, including synaptophysin (SYN) and growth-associated protein-43 (GAP-43). Results: Expression levels of both total Cx43 and p-Cx43 were increased after focal cerebral ischemia, peaking at 7 d. Compared with the MCAO group, Gap26 worsened the neurological behavior and decreased the dendritic spine number while GAP-134 improved the neurobehavior and increased the number of dendritic spines. Moreover, Gap26 further destroyed the synaptic structure, concomitant with downregulated SYN and GAP-43, whereas GAP-134 alleviated synaptic destruction and upregulated SYN and GAP-43. Conclusion: These findings suggested that Cx43 or the gap junction was involved in synaptic plasticity, thereby promoting neural recovery after ischemic stroke. Treatments enhancing gap junctions may be potential promising therapeutic measures for neurorehabilitation after ischemic stroke.
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Affiliation(s)
- Kailing Yang
- Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Ying Zhou
- Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lequan Zhou
- Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Fuman Yan
- Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Li Guan
- Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Haimei Liu
- Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wei Liu
- Department of Physiology, School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.,The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
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Zhang Z, Cao X, Bao X, Zhang Y, Xu Y, Sha D. Cocaine- and amphetamine-regulated transcript protects synaptic structures in neurons after ischemic cerebral injury. Neuropeptides 2020; 81:102023. [PMID: 32005500 DOI: 10.1016/j.npep.2020.102023] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 12/05/2019] [Accepted: 01/23/2020] [Indexed: 01/26/2023]
Abstract
Cocaine-regulated and amphetamine-regulated transcript (CART) is a neuropeptide with reported neuroprotective effects in ischemic cerebral injury. However, its mechanism has not yet been elucidated. Herein, we investigated the role and mechanism of CART in synaptic plasticity in neurons after ischemic cerebral stroke. We found that the survival rate of the oxygen-glucose deprivation (OGD) neurons was increased after CART treatment. Moreover, CART treatment significantly attenuated ischemia-induced neuronal synaptic damage and increased synaptophysin expression. In addition, the number of presynaptic vesicles was increased and the postsynaptic density (PSD) was thickened after CART treatment. Mechanistically, CART treatment enhanced the expression of Arc mRNA in a cAMP response element binding protein (CREB) dependent manner in OGD neurons, and blockade of CREB by KG-501 eliminated the protective effect of CART. Collectively, CART protected the synaptic structure in neurons after ischemic cerebral injury by increasing the Arc expression via upregulating p-CREB.
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Affiliation(s)
- Zhi Zhang
- Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiang Cao
- Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Xinyu Bao
- Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yan Zhang
- Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yun Xu
- Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
| | - Dujuan Sha
- Department of Emergency, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
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36
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Yuan M, Bi X. Therapeutic and Diagnostic Potential of microRNAs in Vascular Cognitive Impairment. J Mol Neurosci 2020; 70:1619-1628. [DOI: 10.1007/s12031-020-01597-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 05/14/2020] [Indexed: 12/19/2022]
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Wang G, Han B, Shen L, Wu S, Yang L, Liao J, Wu F, Li M, Leng S, Zang F, Zhang Y, Bai Y, Mao Y, Chen B, Yao H. Silencing of circular RNA HIPK2 in neural stem cells enhances functional recovery following ischaemic stroke. EBioMedicine 2020; 52:102660. [PMID: 32062357 PMCID: PMC7016383 DOI: 10.1016/j.ebiom.2020.102660] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 01/15/2020] [Accepted: 01/22/2020] [Indexed: 02/06/2023] Open
Abstract
Background Circular RNAs (circRNAs) have been reported to be involved in central nervous system (CNS) diseases and to have a close connection with neuronal development. However, the role of circRNAs in neural stem cell (NSC) differentiation and the treatment of ischaemic stroke remains unknown. Methods Ischaemic stroke was induced in mice using transient middle cerebral artery occlusion (tMCAO). NSCs were transducted with circHIPK2 siRNA (si-circHIPK2-NSCs) or vehicle control (si-circCon-NSCs) and microinjected into lateral ventricle of brain at 7 d post-tMCAO. Magnetic resonance imaging (MRI) was used to detect brain damage, and functional deficits were evaluated with sensorimotor behavioural tests. The distribution of the transplanted NSCs was investigated by near-infrared fluorescence imaging (NIF) and immunofluorescence. The neural plasticity of si-circHIPK2-NSCs was verified by western blot and immunofluorescence in vivo and in vitro. Findings We investigated the role of circHIPK2 in NCS differentiation. In vitro, silencing of circHIPK2 facilitated NSCs directionally differentiated to neurons but had no effect on the differentiation to astrocytes. In vivo, microinjected NSCs could migrate to the ischaemic hemisphere after stroke induction. Si-circHIPK2-NSCs increased neuronal plasticity in the ischaemic brain, conferred long-lasting neuroprotection, and significantly reduced functional deficits. Interpretations Si-circHIPK2 regulates NSC differentiation, and microinjection of si-circHIPK2-NSCs exhibits a promising therapeutic strategy to neuroprotection and functional recovery after stroke. Funding The National Key Research and Development Program of China; the International Cooperation and Exchange of the National Natural Science Foundation of China; the National Natural Science Foundation of China; the Jiangsu Innovation & Entrepreneurship Team Program.
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Affiliation(s)
- Guangtian Wang
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Bing Han
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Ling Shen
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Shusheng Wu
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Li Yang
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Jiefeng Liao
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Fangfang Wu
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Mingyue Li
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Shuo Leng
- Department of Radiology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Fengchao Zang
- Department of Radiology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Yuan Zhang
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Ying Bai
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China
| | - Yu Mao
- State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing 210009, China
| | - Bo Chen
- Materials Science and Devices Institute, Suzhou University of Science and Technology, Suzhou 215009, China
| | - Honghong Yao
- Department of Pharmacology, School of Medicine, Southeast University, Nanjing 210009, China; Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210009, China; Co-innovation Centre of Neuroregeneration, Nantong University, Nantong 226001, China.
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Pichiorri F, Mattia D. Brain-computer interfaces in neurologic rehabilitation practice. HANDBOOK OF CLINICAL NEUROLOGY 2020; 168:101-116. [PMID: 32164846 DOI: 10.1016/b978-0-444-63934-9.00009-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The brain-computer interfaces (BCIs) for neurologic rehabilitation are based on the assumption that by retraining the brain to specific activities, an ultimate improvement of function can be expected. In this chapter, we review the present status, key determinants, and future directions of the clinical use of BCI in neurorehabilitation. The recent advancements in noninvasive BCIs as a therapeutic tool to promote functional motor recovery by inducing neuroplasticity are described, focusing on stroke as it represents the major cause of long-term motor disability. The relevance of recent findings on BCI use in spinal cord injury beyond the control of neuroprosthetic devices to restore motor function is briefly discussed. In a dedicated section, we examine the potential role of BCI technology in the domain of cognitive function recovery by instantiating BCIs in the long history of neurofeedback and some emerging BCI paradigms to address cognitive rehabilitation are highlighted. Despite the knowledge acquired over the last decade and the growing number of studies providing evidence for clinical efficacy of BCI in motor rehabilitation, an exhaustive deployment of this technology in clinical practice is still on its way. The pipeline to translate BCI to clinical practice in neurorehabilitation is the subject of this chapter.
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Affiliation(s)
- Floriana Pichiorri
- Neuroelectrical Imaging and Brain Computer Interface Laboratory, Fondazione Santa Lucia IRCCS, Rome, Italy
| | - Donatella Mattia
- Neuroelectrical Imaging and Brain Computer Interface Laboratory, Fondazione Santa Lucia IRCCS, Rome, Italy.
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39
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Nawata K. Risk Factors Affecting Ischemic Stroke: A Potential Side Effect of Antihypertensive Drugs. Health (London) 2020. [DOI: 10.4236/health.2020.125035] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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40
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Gao BY, Xu DS, Liu PL, Li C, Du L, Hua Y, Hu J, Hou JY, Bai YL. Modified constraint-induced movement therapy alters synaptic plasticity of rat contralateral hippocampus following middle cerebral artery occlusion. Neural Regen Res 2020; 15:1045-1057. [PMID: 31823884 PMCID: PMC7034265 DOI: 10.4103/1673-5374.270312] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb. However, the molecular mechanism underlying its efficacy remains unclear. In this study, a middle cerebral artery occlusion (MCAO) rat model was produced by the suture method. Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days, starting from the 7th day after middle cerebral artery occlusion. Day 1 of treatment lasted for 10 minutes at 2 r/min, day 2 for 20 minutes at 2 r/min, and from day 3 onward for 20 minutes at 4 r/min. CatWalk gait analysis, adhesive removal test, and Y-maze test were used to investigate motor function, sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21st day after MCAO. On the 21st day after MCAO, the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay. The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography. The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats, but had no effect on cognitive function. The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3 (Gria3) in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1A, Avpr1a in the middle cerebral artery-occluded rats. In the ipsilateral hippocampus, only Adra2a was downregulated, and there was no significant change in Gria3. Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3, which is an α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor, within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region. The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged. Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion, but had no effect on Synapsin I levels. Besides, we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus. This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats, and suggests that these positive effects occur via the upregulation of the postsynaptic membrane α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression. This study was approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.
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Affiliation(s)
- Bei-Yao Gao
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Dong-Sheng Xu
- Rehabilitation Section, Department of Spine Surgery, Tongji Hospital of Tongji University; Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of Education, Shanghai, China
| | - Pei-Le Liu
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Ce Li
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Liang Du
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yan Hua
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Jian Hu
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Jia-Yun Hou
- Zhongshan Hospital Institute of Clinical Science, Fudan University, Shanghai, China
| | - Yu-Long Bai
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Wang C, Zhang Q, Yu K, Shen X, Wu Y, Wu J. Enriched Environment Promoted Cognitive Function via Bilateral Synaptic Remodeling After Cerebral Ischemia. Front Neurol 2019; 10:1189. [PMID: 31781025 PMCID: PMC6861441 DOI: 10.3389/fneur.2019.01189] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 10/25/2019] [Indexed: 01/10/2023] Open
Abstract
Ischemic stroke is the second leading cause of death worldwide. Ischemia-induced cognitive dysfunction may result in a poor quality of life. Synaptic plasticity plays a key role in cognition promotion. An enriched environment (EE), which can attenuate cognitive deficits in chronic cerebral hypoperfusion, has been shown to facilitate synaptic plasticity. However, the effect of EE on synaptic plasticity in bilateral cerebral hemispheres in stroke remains unclear. This study used a permanent middle cerebral artery occlusion mouse model, which was divided into standard housing and EE groups. The Morris water maze test was performed to detect the cognitive function. Electron microscopy was used to determine the synapse numbers. The expression of SYN and GAP-43 was then quantified by immunofluorescence staining and Western blot analysis. Compared with the standard housing, EE promoted the cognitive function recovery in the mice with stroke. Moreover, EE increased the synapse numbers and the expression of SYN and GAP-43 in both the ipsilateral and contralateral hemispheres (P < 0.05). A further correlation analysis revealed a positive correlation between the cognitive function outcomes and the relative expression of GAP-43 and SYN. Furthermore, the correlation of the expression of GAP-43 and SYN with cognitive function was higher in the contralateral brain than in the ipsilateral brain. In conclusion, an EE may promote cognitive function via bilateral synaptic remodeling after cerebral ischemia. Also, the contralateral brain may play an important role in the recovery of cognitive function.
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Affiliation(s)
- Chuanjie Wang
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.,Department of Rehabilitation Medicine, Jinshan Hospital, Fudan University, Shanghai, China
| | - Qun Zhang
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Kewei Yu
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Xueyan Shen
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Yi Wu
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Junfa Wu
- Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Sun H, Li A, Hou T, Tao X, Chen M, Wu C, Chen S, Zhu L, Liao H. Neurogenesis promoted by the CD200/CD200R signaling pathway following treadmill exercise enhances post-stroke functional recovery in rats. Brain Behav Immun 2019; 82:354-371. [PMID: 31513876 DOI: 10.1016/j.bbi.2019.09.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 08/22/2019] [Accepted: 09/05/2019] [Indexed: 12/13/2022] Open
Abstract
Stroke is a leading cause of long-term disability worldwide; survivors often show sensorimotor and cognitive deficits. Therapeutic exercise is the most common treatment strategy for rehabilitating patients with stroke via augmentation of neurogenesis, angiogenesis, neurotrophic factors expression, and synaptogenesis. Neurogenesis plays important roles in sensorimotor and cognitive functional recovery, and can be promoted by exercise; however, the mechanism underlying this phenomenon remains unclear. In this study, we explored the effects of treadmill exercise on sensorimotor and cognitive functional recovery, as well as the potential molecular mechanisms underlying the promotion of neurogenesis in a rat model of transient middle cerebral artery occlusion (tMCAO). We found that treadmill exercise facilitated sensorimotor and cognitive functional recovery after tMCAO, and that neural stem/progenitor cell proliferation, differentiation, and migration were enhanced in the ipsilateral subventricular and subgranular zones after tMCAO. Meanwhile, the newborn neurons induced by treadmill exercise after tMCAO had the similar function with pre-existing neurons. Treadmill exercise significantly increased CD200 and CD200 receptor (CD200R) levels in the ipsilateral hippocampus and cortex. Further study revealed that treadmill exercise-induced neurogenesis and functional recovery were clearly inhibited, while Il-β and Tnf-α expression were upregulated, following lentivirus (LV)-induced suppression of post-stroke CD200R expression. Consistent with the effect of treadmill exercise, CD200Fc (a CD200R agonist) markedly promoted neurogenesis and functional recovery after stroke. In addition, CD200Fc could further enhance the functional recovery induced by treadmill exercise after stroke. Our results demonstrate the beneficial role of treadmill exercise in promoting neurogenesis and functional recovery via activating the CD200/CD200R signaling pathway and improving the inflammatory environment after stroke. Thus, the CD200/CD200R signaling pathway is a potential therapeutic target for functional recovery after stroke.
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Affiliation(s)
- Hao Sun
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
| | - Ao Li
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
| | - Tingting Hou
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
| | - Xia Tao
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
| | - Mingming Chen
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
| | - Chaoran Wu
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
| | - Shujian Chen
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China
| | - Lingling Zhu
- Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, China; Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
| | - Hong Liao
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China; State Key Laboratory of National Medicines, China Pharmaceutical University, 24 Tongjiaxiang Street, Nanjing 210009, China.
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Erfani M, Ghazi Tabatabaei Z, Sadigh-Eteghad S, Farokhi-Sisakht F, Farajdokht F, Mahmoudi J, Karimi P, Nasrolahi A. Rosa canina L. methanolic extract prevents heat stress-induced memory dysfunction in rats. Exp Physiol 2019; 104:1544-1554. [PMID: 31297904 DOI: 10.1113/ep087535] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 07/09/2019] [Indexed: 12/17/2022]
Abstract
NEW FINDINGS What is the central question of this study? Heat stress has harmful effects on the brain structure and synaptic density via induction of oxidative stress and neuroinflammation, which result in neuronal damage in the hippocampus and thereby cognitive impairments. In this study, we investigate the effect of Rosa canina treatment on cognitive function in heat stress-exposed rats and its underlying mechanisms. What is the main finding and its importance? We show that R. canina improves cognitive deficits induced by heat stress by attenuation of oxidative stress and neuroinflammation and by upregulation of synaptic proteins in the hippocampus. ABSTRACT The aim of the study was to evaluate the effects of aqueous methanolic extract of Rosa canina (RC) dried fruits on oxidative stress, inflammation, synaptic degeneration and memory dysfunction induced by heat stress (HS) in rats. Sixty adult male Wistar rats were randomly divided into five groups as follows: the control group received normal saline (NS); the HS group was exposed to heat stress (43°C) for 15 min once a day for 2 weeks; and HS+R groups were exposed to heat stress and received one of three doses (250, 500 or 1000 mg kg-1 ) of RC methanolic extract for 2 weeks. A passive avoidance test and a Y-maze test were performed to assess learning and memory. The levels of reactive oxygen species were assessed. The serum cortisol concentration and hippocampal total antioxidant capacity, superoxide dismutase and glutathione peroxidase were also detected using spectrophotometry. The protein expressions of c-Fos, heat-shock protein-70, tumour necrosis factor-α, growth-associated protein 43, post-synaptic density-95 and synaptophysin were evaluated in the hippocampal tissue. The results showed that RC significantly improved cognitive dysfunction induced by HS, which was accompanied by downregulation of tumour necrosis factor-α and upregulation of growth-associated protein 43 and synaptophysin proteins in the hippocampus of HS-exposed rats. Furthermore, RC significantly attenuated serum cortisol concentrations and upregulated heat shock protein-70 and c-Fos in the hippocampus. In addition, the administration of RC attenuated reactive oxygen species levels and enhanced antioxidant defense in the hippocampus. These findings indicate that RC attenuated the deleterious effect of HS on cognition through its antioxidant properties and by enhancing synaptic function and plasticity.
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Affiliation(s)
- Marjan Erfani
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Higher Education Institute of Rab-Rashid, Tabriz, Iran
| | | | - Saeed Sadigh-Eteghad
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Fereshteh Farajdokht
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Mahmoudi
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Pouran Karimi
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ava Nasrolahi
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Biochemistry and Molecular Medicine, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran
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Dual Functions of Microglia in Ischemic Stroke. Neurosci Bull 2019; 35:921-933. [PMID: 31062335 DOI: 10.1007/s12264-019-00388-3] [Citation(s) in RCA: 371] [Impact Index Per Article: 61.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 12/30/2018] [Indexed: 12/16/2022] Open
Abstract
Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However, increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes, and endothelial cells within the brain parenchyma and the neurovascular unit.
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Calabrò RS, Accorinti M, Porcari B, Carioti L, Ciatto L, Billeri L, Andronaco VA, Galletti F, Filoni S, Naro A. Does hand robotic rehabilitation improve motor function by rebalancing interhemispheric connectivity after chronic stroke? Encouraging data from a randomised-clinical-trial. Clin Neurophysiol 2019; 130:767-780. [DOI: 10.1016/j.clinph.2019.02.013] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Revised: 01/28/2019] [Accepted: 02/13/2019] [Indexed: 01/16/2023]
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Rahayu UB, Wibowo S, Setyopranoto I. The Effectiveness of Early Mobilization Time on Balance and Functional Ability after Ischemic Stroke. Open Access Maced J Med Sci 2019; 7:1088-1092. [PMID: 31049086 PMCID: PMC6490474 DOI: 10.3889/oamjms.2019.269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Revised: 04/03/2019] [Accepted: 04/04/2019] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND: Early mobilisation (EM) after-ischemic stroke is a motor learning intervention aimed to restore nerve cells and to improve balance and functional ability. Unfortunately, the study of when this intervention began has not been widely studied. AIM: On this study was compared the effect of EM started at 24 hours and 48 hours after an ischemic stroke on balance and functional ability. MATERIAL AND METHODS: Randomized controlled trial involving 40 patients on 2 groups meeting predefined inclusion criteria. The levels of balance were measured using the Berg Balance Scale, and the functional ability was measured using the Barthel Index, at 5th and 7th day. RESULTS: A significant difference was observed in both balance (p = 0.038) and functional ability (p = 0.021) obtained on the 7th day of assessment between both groups. A significant difference on the 5th day was observed only in the functional ability (p = 0.002) and not in the balance (p = 0.147), between the groups. CONCLUSION: EM started at 24 hours after the ischemic stroke has been found to have a better impact on balance and functional ability compared to that at 48 hours.
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Affiliation(s)
- Umi Budi Rahayu
- Department of Physiotherapy, Faculty of Health Science, Universitas Muhammadiyah Surakarta, Indonesia
| | - Samekto Wibowo
- Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Ismail Setyopranoto
- Department of Neurology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Tong Y, Cheng Z, Rajah GB, Duan H, Cai L, Zhang N, Du H, Geng X, Ding Y. High Intensity Physical Rehabilitation Later Than 24 h Post Stroke Is Beneficial in Patients: A Pilot Randomized Controlled Trial (RCT) Study in Mild to Moderate Ischemic Stroke. Front Neurol 2019; 10:113. [PMID: 30837938 PMCID: PMC6390474 DOI: 10.3389/fneur.2019.00113] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 01/28/2019] [Indexed: 12/13/2022] Open
Abstract
Objective: Very early mobilization was thought to contribute to beneficial outcomes in stroke-unit care, but the optimal intervention strategy including initiation time and intensity of mobilization are unclear. In this study, we sought to confirm the rehabilitative effects of different initiation times (24 vs. 48 h) with different mobilization intensities (routine or intensive) in ischemic stroke patients within three groups. Materials and Methods: We conducted a randomized and controlled trial with a blinded follow-up assessment. Patients with ischemic stroke, first or recurrent, admitted to stroke unit within 24 h after stroke onset were recruited. Eligible subjects were randomly assigned (1:1:1) to 3 groups: Early Routine Mobilization in which patients received < 1.5 h/d out-of-bed mobilization within 24-48 h after stroke onset, Early Intensive Mobilization in which patients initiated ≥3 h/d mobilization at 24-48 h after the stroke onset, and Very Early Intensive Mobilization in which patients received≥3 h/d mobilization within 24 h. The modified Rankin Scale score of 0-2 was used as the primary favorable outcome. Results: We analyzed 248 of the 300 patients (80 in Early Routine Mobilization, 82 in Very Early Intensive Mobilization and 86 in Early Intensive Mobilization), with 52 dropping out (20 in Early Routine Mobilization, 18 in Very Early Intensive Mobilization and 14 in Early Intensive Mobilization). Among the three groups, the Early Intensive Mobilization group had the most favorable outcomes at 3-month follow-up, followed by patients in the Early Routine Mobilization group. Patients in Very Early Intensive Mobilization received the least odds of favorable outcomes. At 3 month follow up, 53.5%, (n = 46) of patients with Early Intensive Mobilization showed a favorable outcome (modified Rankin Scale 0-2) (p = 0.041) as compared to 37.8% (n = 31) of patients in the Very Early Intensive Mobilization. Conclusions: Post-stroke rehabilitation with high intensity physical exercise at 48 h may be beneficial. Very Early Intensive Mobilization did not lead to a favorable outcome at 3 months. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR-ICR-15005992.
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Affiliation(s)
- Yanna Tong
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
| | - Zhe Cheng
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
| | - Gary B. Rajah
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
| | - Honglian Duan
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
| | - Lipeng Cai
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
| | - Nan Zhang
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
| | - Huishan Du
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
| | - Xiaokun Geng
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurology, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
| | - Yuchuan Ding
- China-America Institute of Neuroscience, Beijing Luhe Hospital, Affiliated to Capital Medical University, Beijing, China
- Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, United States
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Lunghi C, Sframeli AT, Lepri A, Lepri M, Lisi D, Sale A, Morrone MC. A new counterintuitive training for adult amblyopia. Ann Clin Transl Neurol 2019; 6:274-284. [PMID: 30847360 PMCID: PMC6389748 DOI: 10.1002/acn3.698] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 10/22/2018] [Accepted: 10/23/2018] [Indexed: 12/23/2022] Open
Abstract
Objectives The aim of this study was to investigate whether short-term inverse occlusion, combined with moderate physical exercise, could promote the recovery of visual acuity and stereopsis in a group of adult anisometropic amblyopes. Methods Ten adult anisometropic patients underwent six brief (2 h) training sessions over a period of 4 weeks. Each training session consisted in the occlusion of the amblyopic eye combined with physical exercise (intermittent cycling on a stationary bike). Visual acuity (measured with ETDRS charts), stereoacuity (measured with the TNO test), and sensory eye dominance (measured with binocular rivalry) were tested before and after each training session, as well as in follow-up visits performed 1 month, 3 months, and 1 year after the end of the training. Results After six brief (2 h) training sessions, visual acuity improved in all 10 patients (0.15 ± 0.02 LogMar), and six of them also recovered stereopsis. The improvement was preserved for up to 1 year after training. A pilot experiment suggested that physical activity might play an important role for the recovery of visual acuity and stereopsis. Conclusions Our results suggest a noninvasive training strategy for adult human amblyopia based on an inverse-occlusion procedure combined with physical exercise.
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Affiliation(s)
- Claudia Lunghi
- Department of Translational Research on New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
- Laboratoire des systèmes perceptifsDépartement d’études cognitivesÉcole normale supérieurePSL UniversityCNRS75005ParisFrance
| | - Angela T. Sframeli
- Ophthalmology UnitDepartment of Surgical, Medical, Molecular and Critical Area PathologyUniversity of PisaPisaItaly
| | - Antonio Lepri
- Ophthalmology UnitDepartment of Surgical, Medical, Molecular and Critical Area PathologyUniversity of PisaPisaItaly
| | - Martina Lepri
- Ophthalmology UnitDepartment of Surgical, Medical, Molecular and Critical Area PathologyUniversity of PisaPisaItaly
| | - Domenico Lisi
- Ophthalmology UnitDepartment of Surgical, Medical, Molecular and Critical Area PathologyUniversity of PisaPisaItaly
| | - Alessandro Sale
- Neuroscience InstituteNational Research Council (CNR)PisaItaly
| | - Maria C. Morrone
- Department of Translational Research on New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
- IRCCS Stella MarisCalambronePisaItaly
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Shen Y, Park JB, Lee SY, Han SK, Ryu PD. Exercise training normalizes elevated firing rate of hypothalamic presympathetic neurons in heart failure rats. Am J Physiol Regul Integr Comp Physiol 2018; 316:R110-R120. [PMID: 30485115 DOI: 10.1152/ajpregu.00225.2018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Exercise training (ExT) normalizes elevated sympathetic nerve activity in heart failure (HF), but the underlying mechanisms are not well understood. In this study, we examined the effects of 3 wk of ExT on the electrical activity of the hypothalamic presympathetic neurons in the brain slice of HF rats. HF rats were prepared by ligating the left descending coronary artery. The electrophysiological properties of paraventricular nucleus neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) were examined using the slice patch-clamp technique. The neuronal firing rate was elevated in HF rats, and ExT induced a reduction in the firing rate ( P < 0.01). This ExT-induced decrease in the firing rate was associated with an increased frequency of spontaneous and miniature inhibitory postsynaptic current (IPSCs; P < 0.05). There was no significant change in excitatory postsynaptic current. Replacing Ca2+ with Mg2+ in the recording solution reduced the elevated IPSC frequency in HF rats with ExT ( P < 0.01) but not in those without ExT, indicating an increase in the probability of GABA release. In contrast, ExT did not restore the reduced GABAA receptor-mediated tonic inhibitory current in HF rats. A GABAA receptor blocker (bicuculline, 20 μM) increased the firing rate in HF rats with ExT ( P < 0.01) but not in those without ExT. Collectively, these results show that ExT normalized the elevated firing activity by increasing synaptic GABA release in PVN-RVLM neurons in HF rats. Our findings provide a brain mechanism underlying the beneficial effects of ExT in HF, which may shed light on the pathophysiology of other diseases accompanied by sympathetic hyperactivation.
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Affiliation(s)
- Yiming Shen
- Department of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University , Seoul , Republic of Korea
| | - Jin Bong Park
- Department of Physiology, School of Medicine, Chungnam National University , Daejeon , Republic of Korea
| | - So Yeong Lee
- Department of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University , Seoul , Republic of Korea
| | - Seong Kyu Han
- Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Republic of Korea
| | - Pan Dong Ryu
- Department of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University , Seoul , Republic of Korea
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Wang H, Gaur U, Xiao J, Xu B, Xu J, Zheng W. Targeting phosphodiesterase 4 as a potential therapeutic strategy for enhancing neuroplasticity following ischemic stroke. Int J Biol Sci 2018; 14:1745-1754. [PMID: 30416389 PMCID: PMC6216030 DOI: 10.7150/ijbs.26230] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 06/03/2018] [Indexed: 12/11/2022] Open
Abstract
Sensorimotor recovery following ischemic stroke is highly related with structural modification and functional reorganization of residual brain tissues. Manipulations, such as treatment with small molecules, have been shown to enhance the synaptic plasticity and contribute to the recovery. Activation of the cAMP/CREB pathway is one of the pivotal approaches stimulating neuroplasticity. Phosphodiesterase 4 (PDE4) is a major enzyme controlling the hydrolysis of cAMP in the brain. Accumulating evidences have shown that inhibition of PDE4 is beneficial for the functional recovery after cerebral ischemia; i. subtype D of PDE4 (PDE4D) is viewed as a risk factor for ischemic stroke; ii. inhibition of PDE4 enhances neurological behaviors, such as learning and memory, after stroke in rodents; iii.PDE4 inhibition increases dendritic density, synaptic plasticity and neurogenesis; iv. activation of cAMP/CREB signaling by PDE4 inhibition causes an endogenous increase of BDNF, which is a potent modulator of neuroplasticity; v. PDE4 inhibition is believed to restrict neuroinflammation during ischemic stroke. Cumulatively, these findings provide a link between PDE4 inhibition and neuroplasticity after cerebral ischemia. Here, we summarized the possible roles of PDE4 inhibition in the recovery of cerebral stroke with an emphasis on neuroplasticity. We also made some recommendations for future research.
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Affiliation(s)
- Haitao Wang
- Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Uma Gaur
- Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Jiao Xiao
- Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Bingtian Xu
- Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jiangping Xu
- Department of Neuropharmacology and Drug Discovery, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Wenhua Zheng
- Faculty of Health Sciences, University of Macau, Taipa, Macau, China
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