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      Effects of melatonin-pretreated adipose-derived mesenchymal stem cells (MSC) in an animal model of spinal cord injury

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          Abstract

          Background

          One of the most serious nervous system diseases is spinal cord injury(SCI), which is increasing for various reasons. Although no definitive treatment has yet been identified for SCI, one possible treatment is adipose-derived stem cells(ADSCs). However, a key issue in transplantation is improving cells’ survival and function in the target tissue. Melatonin(MT) hormone with antioxidant properties can prolong cell survival and improve cell function. This study investigates the pre-conditioning of ADSCs with melatonin for enhancing the engraftment and neurological function of rats undergoing SCI.

          Methods

          42 male Sprague–Dawley rats were divided into six groups, including Control, Sham, Model, Vehicle, and Lesion treatments A and B. After acquiring white adipose tissue, stem cells were evaluated by flow cytometry. SCI was then applied in Model, Vehicle, A, and B groups. Group A and B received ADSCs and ADSCs + melatonin, respectively, 1 week after SCI, but the vehicle received only an intravenous injection for simulation; The other groups were recruited for the behavioral test. Immunohistochemistry(IHC) was used to assess the engraftment and differentiation of ADSCs in the SCI site. Basso, Beattie, and Bresnahan's score was used to evaluate motor function between the six groups.

          Results

          Histological studies and cell count confirmed ADSCs implantation at the injury site, which was higher in the MT-ADSCs (P < 0.001). IHC revealed the differentiation of ADSCs and MT-ADSCs into neurons, astrocytes, and oligodendrocyte lineage cells, which were higher in MT-ADSCs. Functional improvement was observed in SCI + ADSCs and SCI + MT-ADSCs groups.

          Conclusion

          The pre-conditioning of ADSCs with melatonin positively affects engraftment and neuronal differentiation in SCI but does not impact performance improvement compared to the ADSCs.

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          Most cited references36

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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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            Spinal Cord Injury: Pathophysiology, Multimolecular Interactions, and Underlying Recovery Mechanisms

            Spinal cord injury (SCI) is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions. Its pathophysiology comprises acute and chronic phases and incorporates a cascade of destructive events such as ischemia, oxidative stress, inflammatory events, apoptotic pathways and locomotor dysfunctions. Many therapeutic strategies have been proposed to overcome neurodegenerative events and reduce secondary neuronal damage. Efforts have also been devoted in developing neuroprotective and neuro-regenerative therapies that promote neuronal recovery and outcome. Although varying degrees of success have been achieved, curative accomplishment is still elusive probably due to the complex healing and protective mechanisms involved. Thus, current understanding in this area must be assessed to formulate appropriate treatment modalities to improve SCI recovery. This review aims to promote the understanding of SCI pathophysiology, interrelated or interlinked multimolecular interactions and various methods of neuronal recovery i.e., neuroprotective, immunomodulatory and neuro-regenerative pathways and relevant approaches.
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              Cell transplantation therapy for spinal cord injury

              The consequences of spinal cord injury are often severe and irreversible; cell transplantation has emerged as a potential treatment. In this Review, the authors highlight mechanisms through which cell transplantation is thought to promote functional improvements and the obstacles to making cell transplantation a viable therapy.
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                Author and article information

                Contributors
                Arvin_naeimi@yahoo.com
                Zaminy_a@yahoo.com
                amini_ot@yahoo.com
                raziye.sani15562@yahoo.com
                masoomeh_golipoor@yahoo.com
                Journal
                BMC Neurosci
                BMC Neurosci
                BMC Neuroscience
                BioMed Central (London )
                1471-2202
                16 November 2022
                16 November 2022
                2022
                : 23
                : 65
                Affiliations
                [1 ]GRID grid.411874.f, ISNI 0000 0004 0571 1549, Student Research Committee, School of Medicine, , Guilan University of Medical Sciences, ; Rasht, Iran
                [2 ]GRID grid.411874.f, ISNI 0000 0004 0571 1549, Burn and Regenerative Medicine Research Center, Velayat Hospital, School of Medicine, , Guilan University of Medical Sciences, ; Rasht, Iran
                [3 ]GRID grid.411746.1, ISNI 0000 0004 4911 7066, Cellular and Molecular Research Center, , Iran University of Medical Sciences, ; Tehran, Iran
                [4 ]GRID grid.411874.f, ISNI 0000 0004 0571 1549, Cellular and Molecular Research Center, Faculty of Medicine, , Guilan University of Medical Sciences, ; Rasht, Iran
                Author information
                https://orcid.org/0000-0002-8659-9549
                https://orcid.org/0000-0001-9661-0636
                Article
                752
                10.1186/s12868-022-00752-6
                9667651
                36384473
                b35b4d64-87d4-4909-9e7e-5a0d8c0c10cb
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 15 July 2022
                : 4 November 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100005421, Guilan University of Medical Sciences;
                Categories
                Research
                Custom metadata
                © The Author(s) 2022

                Neurosciences
                melatonin,adipose-derived mesenchymal stem cells,mesenchymal stem cells,spinal cord injury,pretreatment,animal model,sci,adsc,msc

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