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      Effect of Electro-Acupuncture on Neuroplasticity of Spinal Cord-Transected Rats

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          Abstract

          Background

          This study aimed to evaluate the effects of electro-acupuncture (EA) on neuroplasticity associated with the expressions of neurotrophic factors (NTFs) and their receptors in rats subjected to spinal cord transection (SCT).

          Material/Methods

          A total of 144 rats were randomly divided into 3 groups (n=48 per group): sham-operated group, SCT group, and EA (electro-acupuncture) group. Rats in SCT and EA groups received spinal cord transection at T 10–T 11 vertebral levels. Then, EA group rats received EA treatment. Reverse transcription polymerase chain reaction was used to detect NTFs and receptors at the mRNA level. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect the expression of NTFs and their receptors. Basso, Beattie, Bresnahan (BBB) scores and cortical somato-sensory evoked potentials (CSEP) were evaluated to assess the recovery of motor and sensory functions. We also measured BDA (Biotinylated dextran amine) axonal tracing, CGRP (Calcitonin gene-related peptide), GAP-43 (Growth-associated protein), and synaptophysin immunohistochemistry (IHC).

          Results

          EA treatment led to obvious improvement in hindlimb locomotor and sensory functions. CNTF, FGF-2, and TrkB mRNA were significantly upregulated, while NGF, PDGF, TGF-β1, IGF-1, TrkA, and TrkC mRNA were concomitantly downregulated in the caudal spinal segment (CSS) following EA. Immunohistochemistry demonstrated an increased number of CGRP fibers, GAP-43, and synaptophysin profiles in the CSS in the EA rats.

          Conclusions

          EA may promote the recovery of neuroplasticity in rats subjected to SCT. This could be attributed to the systematic regulation of NTFs and their receptors after EA.

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          Most cited references25

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          cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury.

          Central neurons regenerate axons if a permissive environment is provided; after spinal cord injury, however, inhibitory molecules are present that make the local environment nonpermissive. A promising new strategy for inducing neurons to overcome inhibitory signals is to activate cAMP signaling. Here we show that cAMP levels fall in the rostral spinal cord, sensorimotor cortex and brainstem after spinal cord contusion. Inhibition of cAMP hydrolysis by the phosphodiesterase IV inhibitor rolipram prevents this decrease and when combined with Schwann cell grafts promotes significant supraspinal and proprioceptive axon sparing and myelination. Furthermore, combining rolipram with an injection of db-cAMP near the graft not only prevents the drop in cAMP levels but increases them above those in uninjured controls. This further enhances axonal sparing and myelination, promotes growth of serotonergic fibers into and beyond grafts, and significantly improves locomotion. These findings show that cAMP levels are key for protection, growth and myelination of injured CNS axons in vivo and recovery of function.
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            Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury.

            Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory, and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed toward regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neuroregenerative recovery is possible and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI.
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              Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1.

              Transgenic mice overexpressing the chemokine monocyte chemoattractant protein-1 (MCP-1) in the thymus and central nervous system have a higher number of mononuclear cells in those tissues than do control littermates. In the thymus, there is a modest increase in the number of Mac-1 and F4/80 positive cells, but no apparent change in the number of lymphoid cells. A more pronounced mononuclear infiltrate is detected in transgenic mice expressing MCP-1 in the brain. The vast majority of the recruited cells in the brain are monocytes and macrophages, as defined by light microscopy, and ultrastructural and immunohistochemical criteria. Such cells are found in a perivascular orientation with minimal parenchymal infiltration, possibly as a consequence of the accumulation of MCP-1 in the vessels, as shown by immunohistochemistry. The mononuclear cell infiltrate in the brain can be significantly amplified by LPS treatment, suggesting that the recruitment properties of MCP-1 can be potentiated by additional factors.
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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
                2017
                02 September 2017
                : 23
                : 4241-4251
                Affiliations
                [1 ]Department of Neurosurgery, Shanghai Jiao Tong University Affiliated 6 th People’s Hospital, Shanghai, P.R. China
                [2 ]Department of Neurology, ZhongDa Hospital, Neuropsychiatric Institute, Medical School of Southeast University, Nanjing, Jiangsu, P.R. China
                Author notes
                Corresponding Authors: Hengli Tian, e-mail: tianhengli1964@ 123456yahoo.com.cn and Xiaoli Li, e-mail: xiaolili2016vip@ 123456163.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                [*]

                Co-first authors

                Article
                903056
                10.12659/MSM.903056
                5592974
                28865235
                fa51f8b2-37e9-471b-bd7a-b08c6c89ef6b
                © Med Sci Monit, 2017

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

                History
                : 27 December 2016
                : 11 February 2017
                Categories
                Animal Study

                electroacupuncture,immunohistochemistry,neurotrophic factor,spinal cord neuroplasticity

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