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Deferoxamine Ameliorates Compressed Spinal Cord Injury by Promoting Neovascularization in Rats

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Abstract

The therapeutic effect of deferoxamine (DFO) for spinal cord injury (SCI) has been demonstrated in previous studies; however, the exact mechanism of action is still unclear. Here, we hypothesized that DFO ameliorates spinal cord compression by promoting neovascularization. Using an SCI model of moderate compression, rats were intraperitoneally injected with 30 mg/kg or 100 mg/kg DFO for 1–2 weeks, and significant neovascularization was found in the injured spinal cord, showing overexpression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), and an increase in the number of new blood vessels. In addition, SCI in rats was significantly ameliorated after treatment with DFO, with less motor dysfunction, increased spared neural tissue, and improved electrophysiological conduction. By contrast, the ameliorative effect of DFO on SCI was suppressed when DFO-induced neovascularization was blocked by lenvatinib, a vascular endothelial growth factor receptor inhibitor, further suggesting that the primary pharmacological effect of DFO in SCI is the promotion of neovascularization. Therefore, we concluded that DFO effectively alleviated SCI by promoting neovascularization in the injured spinal cord. Considering that DFO is an FDA-approved free radical scavenger and iron chelator, it may represent a promising alternative strategy for SCI therapy in the future.

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Availability of Data and Material

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

This work was supported by the Natural Science Foundation of Jiangsu Province (No. BK20161274), the Natural Science Foundation of Suzhou (No. kjxw2015056) and the Science and Technology Bureau of Kunshan (No. KS1547). We would also like to thank LetPub for providing linguistic assistance during the preparation of this manuscript.

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Authors and Affiliations

  1. Orthopedic Center, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215000, China

    Guoqing Tang & Weimin Jiang

  2. Orthopedic center, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Suzhou, China

    Guoqing Tang, Yong Chen & Ji Chen

  3. Department of Orthopedic, RuiJin Hospital, School of Medicine, Shanghai Jiao-tong University, Shanghai, China

    Zhe Chen

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  1. Guoqing Tang
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  2. Yong Chen
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  3. Ji Chen
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  4. Zhe Chen
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  5. Weimin Jiang
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Correspondence to Weimin Jiang.

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All experimental procedures were performed in accordance with protocols approved by the Animal Ethics Committee of Soochow University, Suzhou, China.

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Tang, G., Chen, Y., Chen, J. et al. Deferoxamine Ameliorates Compressed Spinal Cord Injury by Promoting Neovascularization in Rats. J Mol Neurosci 70, 1437–1444 (2020). https://doi.org/10.1007/s12031-020-01564-1

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  • DOI: https://doi.org/10.1007/s12031-020-01564-1

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