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      A Novel Acute Discogenic Myelopathy Model Using Merocel ® Sponge: Comparison With Clip Compression Model in Rats

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          Abstract

          Objective

          Animal models of spinal cord injuries (SCIs) use rats to simulate human SCIs. Among the various techniques, clips have been used to reproduce the compression-contusion model. However, the mechanism of injury in discogenic incomplete SCI may differ from that in clip injury; however, a model has yet to be established. Previously, we issued a patent (No. 10-2053770) for a rat SCI model using Merocel ®, a water-absorbing self-expanding polymer sponge. The objectives of this study were to compare the locomotor and histopathological changes between the Merocel ®-compression model (MC group) and clip compression model (clip group).

          Methods

          This study included 4 groups of rats: MC (n=30), MC-sham (n=5), clip (n=30), and clip-sham (n=5). Locomotor function was evaluated in all groups using the Basso, Beattie, and Bresnahan (BBB) scoring system, 4 weeks after injury. Histopathological analyses included morphology, presence of inflammatory cells, microglial activation, and extent of neuronal damage, which were compared among the groups.

          Results

          The BBB scores in the MC group were significantly higher than those in the clip group throughout the 4 weeks ( p<0.01). Neuropathological changes in the MC group were significantly less severe than those in the clip group. In addition, motor neurons were well preserved in the ventral horn of the MC group but poorly preserved in the ventral horn of the clip group.

          Conclusion

          The novel MC group can help elucidate the pathophysiology of acute discogenic incomplete SCIs and may be applied in various SCI therapeutic strategies.

          GRAPHICAL ABSTRACT

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          Most cited references35

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          Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection.

          Injury reproducibility is an important characteristic of experimental models of spinal cord injuries (SCI) because it limits the variability in locomotor and anatomical outcome measures. Recently, a more sensitive locomotor rating scale, the Basso, Beattie, and Bresnahan scale (BBB), was developed but had not been tested on rats with severe SCI complete transection. Rats had a 10-g rod dropped from heights of 6.25, 12.5, 25, and 50 mm onto the exposed cord at Tl 0 using the NYU device. A subset of rats with 25 and 50 mm SCI had subsequent spinal cord transection (SCI + TX) and were compared to rats with transection only (TX) in order to ascertain the dependence of recovery on descending systems. After 7-9 weeks of locomotor testing, the percentage of white matter measured from myelin-stained cross sections through the lesion center was significantly different between all the groups with the exception of 12.5 vs 25 mm and 25 vs 50 mm groups. Locomotor recovery was greatest for the 6.25-mm group and least for the 50-mm group and was correlated positively to the amount of tissue sparing at the lesion center (p 0.05). Thus, spared descending systems appear to modify segmental systems which produce greater behavioral improvements than isolated cord systems.
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            Repertoire of microglial and macrophage responses after spinal cord injury.

            Macrophages from the peripheral circulation and those derived from resident microglia are among the main effector cells of the inflammatory response that follows spinal cord trauma. There has been considerable debate in the field as to whether the inflammatory response is good or bad for tissue protection and repair. Recent studies on macrophage polarization in non-neural tissues have shed much light on their changing functional states. In the context of this literature, we discuss the activation of macrophages and microglia following spinal cord injury, and their effects on repair. Harnessing their anti-inflammatory properties could pave the way for new therapeutic strategies for spinal cord trauma.
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              Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products.

              Alternative processing of RNA transcripts from the calcitonin gene results in the production of distinct mRNAs encoding the hormone calcitonin or a predicted product referred to as calcitonin gene-related peptide (CGRP). The calcitonin mRNA predominates in the thyroid while the CGRP-specific mRNA appears to predominate in the hypothalamus. These observations lead us to propose a model in which developmental regulation of RNA processing is used to increase the diversity of neuroendocrine gene expression.
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                Author and article information

                Journal
                Korean J Neurotrauma
                Korean J Neurotrauma
                KJN
                Korean Journal of Neurotrauma
                Korean Neurotraumatology Society
                2234-8999
                2288-2243
                June 2023
                23 June 2023
                : 19
                : 2
                : 204-217
                Affiliations
                [1 ]Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.
                [2 ]Department of Neurosurgery, College of Medicine, Jeju National University, Jeju, Korea.
                Author notes
                Address for correspondence: Ki-Bum Sim. Department of Neurosurgery, College of Medicine, Jeju National University, 15 Aran 13-gil, Jeju 63241, Korea. kibumsim@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-3485-6101
                https://orcid.org/0000-0002-2281-1221
                Article
                10.13004/kjnt.2023.19.e28
                10329878
                2a1d1fec-1307-4d81-97ca-97894a822187
                Copyright © 2023 Korean Neurotraumatology Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 March 2023
                : 02 June 2023
                : 08 June 2023
                Funding
                Funded by: National Research Foundation of Korea, CrossRef https://doi.org/10.13039/501100003725;
                Award ID: NRF-2014R1A1A2055965
                Categories
                Current Issue
                Laboratory Investigation

                animal model,rat,spinal cord injury,spinal cord compression

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