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      Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) and Treadmill Training on Recovery of Motor Function in a Rat Model of Partial Spinal Cord Injury

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          Abstract

          Background

          This study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) and treadmill training (TT) on motor function recovery in rats with partial spinal cord injury (SCI).

          Material/Methods

          Sixty rats with moderate partial SCI at the 9 th thoracic vertebral level induced by a Louisville Injury System Apparatus impactor were randomly allocated to 5 groups: Sham surgery (Intact); Sham rTMS without TT (S-rTMS/Non-TT); Sham rTMS with TT (S-rTMS/TT); rTMS without TT (rTMS/Non-TT); and rTMS with TT (rTMS/TT). Interventions commenced 8 days after SCI and continued for 8 weeks. Outcomes studied were Basso, Beattie, and Bresnahan locomotor scale scores, grid walking test, and biochemical analysis of the brain-derived neurotrophic factor (BDNF), synapsin I (SYN), and postsynaptic density protein-95 (PSD-95) in the motor cortex and spinal cord.

          Results

          The rTMS/TT contributed to greater Basso, Beattie, and Bresnahan scores compared with the S-rTMS/Non-TT ( P<0.01), S-rTMS/TT ( P<0.05), and rTMS/Non-TT ( P<0.05), and showed obviously reduced numbers of foot drops compared with the S-rTMS/Non-TT ( P<0.05). The rTMS/TT significantly increased the expressions of BDNF, SYN, and PSD-95 compared with the S-rTMS/Non-TT, both in the motor cortex ( P<0.01, P<0.01, P<0.001, respectively) and spinal cord ( P<0.001, P<0.01, P<0.05, respectively).

          Conclusions

          In a modified rat model of SCI, combined rTMS with TT improved motor function, indicating that this combined approach promoted adaptive neuroplasticity between the motor cortex and the spinal cord. A combined app roach to improving motor function following SCI requires further evaluation to determine the possible clinical applications.

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          Most cited references55

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          A sensitive and reliable locomotor rating scale for open field testing in rats.

          Behavioral assessment after spinal cord contusion has long focused on open field locomotion using modifications of a rating scale developed by Tarlov and Klinger (1954). However, on-going modifications by several groups have made interlaboratory comparison of locomotor outcome measures difficult. The purpose of the present study was to develop an efficient, expanded, and unambiguous locomotor rating scale to standardize locomotor outcome measures across laboratories. Adult rats (n = 85) were contused at T7-9 cord level with an electromagnetic or weight drop device. Locomotor behavior was evaluated before injury, on the first or second postoperative day, and then for up to 10 weeks. Scoring categories and attributes were identified, operationally defined, and ranked based on the observed sequence of locomotor recovery patterns. These categories formed the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale. The data indicate that the BBB scale is a valid and predictive measure of locomotor recovery able to distinguish behavioral outcomes due to different injuries and to predict anatomical alterations at the lesion center. Interrater reliability tests indicate that examiners with widely varying behavioral testing experience can apply the scale consistently and obtain similar scores. The BBB Locomotor Rating Scale offers investigators a more discriminating measure of behavioral outcome to evaluate treatments after spinal cord injury.
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            BDNF and activity-dependent synaptic modulation.

            Bai Lu (2003)
            It is widely accepted that neuronal activity plays a pivotal role in synaptic plasticity. Neurotrophins have emerged recently as potent factors for synaptic modulation. The relationship between the activity and neurotrophic regulation of synapse development and plasticity, however, remains unclear. A prevailing hypothesis is that activity-dependent synaptic modulation is mediated by neurotrophins. An important but unresolved issue is how diffusible molecules such as neurotrophins achieve local and synapse-specific modulation. In this review, I discuss several potential mechanisms with which neuronal activity could control the synapse-specificity of neurotrophin regulation, with particular emphasis on BDNF. Data accumulated in recent years suggest that neuronal activity regulates the transcription of BDNF gene, the transport of BDNF mRNA and protein into dendrites, and the secretion of BDNF protein. There is also evidence for activity-dependent regulation of the trafficking of the BDNF receptor, TrkB, including its cell surface expression and ligand-induced endocytosis. Further study of these mechanisms will help us better understand how neurotrophins could mediate activity-dependent plasticity in a local and synapse-specific manner.
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              Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer

              Brain-derived neurotrophic factor (BDNF) is one of the most distributed and extensively studied neurotrophins in the mammalian brain. BDNF signals through the tropomycin receptor kinase B (TrkB) and the low affinity p75 neurotrophin receptor (p75NTR). BDNF plays an important role in proper growth, development, and plasticity of glutamatergic and GABAergic synapses and through modulation of neuronal differentiation, it influences serotonergic and dopaminergic neurotransmission. BDNF acts as paracrine and autocrine factor, on both pre-synaptic and post-synaptic target sites. It is crucial in the transformation of synaptic activity into long-term synaptic memories. BDNF is considered an instructive mediator of functional and structural plasticity in the central nervous system (CNS), influencing dendritic spines and, at least in the hippocampus, the adult neurogenesis. Changes in the rate of adult neurogenesis and in spine density can influence several forms of learning and memory and can contribute to depression-like behaviors. The possible roles of BDNF in neuronal plasticity highlighted in this review focus on the effect of antidepressant therapies on BDNF-mediated plasticity. Moreover, we will review data that illustrate the role of BDNF as a potent protective factor that is able to confer protection against neurodegeneration, in particular in Alzheimer’s disease. Finally, we will give evidence of how the involvement of BDNF in the pathogenesis of brain glioblastoma has emerged, thus opening new avenues for the treatment of this deadly cancer.
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                Author and article information

                Journal
                Med Sci Monit
                Med Sci Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2021
                25 July 2021
                08 April 2021
                : 27
                : e931601-1-e931601-13
                Affiliations
                [1 ]School of Rehabilitation Medicine, Nanjing Medical University, Center of Rehabilitation Medicine, 1 st affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China
                [2 ]Department of Rehabilitation Medicine, Jiangsu Shengze Hospital, Nanjing Medical University, Suzhou, Jiangsu, PR China
                [3 ]Department of Rehabilitation Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, PR China
                [4 ]Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu, PR China
                [5 ]Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, PR China
                Author notes
                Corresponding Authors: Guangxu Xu, e-mail: xuguangxu1@ 123456126.com , Hongxing Wang, e-mail: hongxingwangphd@ 123456aol.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                931601
                10.12659/MSM.931601
                8317583
                34304239
                c0d32cd7-6af8-4baa-9ee8-9235d7e13aa1
                © Med Sci Monit, 2021

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 13 February 2021
                : 24 March 2021
                Categories
                Animal Study

                neuronal plasticity,spinal cord injuries,transcranial magnetic stimulation

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