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Demyelination Occurred as the Secondary Damage Following Diffuse Axonal Loss in a Rat Model of Radiation Myelopathy

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Abstract

The main purpose of the present study was to examine the time and dose-dependent course of demyelination in the rat radiation myelopathy model in the first 180 days after irradiation of the spinal cord. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60Co irradiator to deliver 50 Gy and 100 Gy, respectively. The behavioral dysfunction was observed by the forelimb paralysis scoring system. The histological damage in the irradiated spinal cord was examined by hematoxylin/eosin staining, luxol fast blue staining, immunohistochemical analysis, methylene blue/Azure II staining, and uranyl/lead salts staining. The gene expression of oligodendrocyte-related markers were also determined by quantitative real-time PCR. The complete loss of forelimb motor function in all animals was observed at 180 days 50 Gy post-irradiation and at 120 days 100 Gy post-irradiation. We demonstrated that a 50 and 100-Gy single-dose irradiation of the C2-T2 spinal cord segment resulted in diffuse axonal loss and elicited secondary demyelination damage in the spinal cord. We further observed that 100-Gy irradiation reduced the gene expression of myelin oligodendrocyte glycoprotein in irradiated spinal cord. Taken together, our data not only define diffuse axonal loss as the main histological damage but also provide the first evidence that demyelination occurred as the secondary damage in irradiated spinal cord.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81670180, 81370077, 81001220 and 81202090), NIG Collaborative Research Program (2016-A2-4), the Chongqing Science and Technology Committee (CSTC2016JCYJA0083 and 2016CSTCJBKY01702), Beijing Municipal Science and Technology Commission, and Chongqing Municipal Commission of Health and Family Planning (2016MSXM103). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, 400020, China

    Li Wei & Chang-Jiang Liu

  2. Department of Oncology, Tai He Hospital, Shiyan, Hubei, 442000, China

    Yong Zhou

  3. Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Ke Zheng

  4. Affiliated Hospital of the Academy of Military Medical Sciences, Beijing, 100071, China

    Hua You

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  1. Li Wei
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  2. Yong Zhou
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  3. Chang-Jiang Liu
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  4. Ke Zheng
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  5. Hua You
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Correspondence to Hua You.

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Wei, L., Zhou, Y., Liu, CJ. et al. Demyelination Occurred as the Secondary Damage Following Diffuse Axonal Loss in a Rat Model of Radiation Myelopathy. Neurochem Res 42, 953–962 (2017). https://doi.org/10.1007/s11064-016-2128-1

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