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Valproic acid reduces autophagy and promotes functional recovery after spinal cord injury in rats

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Abstract

Secondary damage is a critical determinant of the functional outcome in patients with spinal cord injury (SCI), and involves multiple mechanisms of which the most important is the loss of nerve cells mediated by multiple factors. Autophagy can result in cell death, and plays a key role in the development of SCI. It has been recognized that valproic acid (VPA) is neuroprotective in certain experimental animal models, however, the levels of autophagic changes in the process of neuroprotection by VPA treatment following SCI are still unknown. In the present study, we determined the extent of autophagy after VPA treatment in a rat model of SCI. We found that both the mRNA and protein levels of Beclin-1 and LC3 were significantly increased at 1, 2, and 6 h after SCI and peaked at 2 h; however, Western blot showed that autophagy was markedly decreased by VPA treatment at 2 h post-injury. Besides, post-SCI treatment with VPA improved the Basso-Beattie-Bresnahan scale, increased the number of ventral horn motoneurons, and reduced myelin sheath damage compared with vehicle-treated animals at 42 days after SCI. Together, our results demonstrated the characteristics of autophagy expression following SCI, and found that VPA reduced autophagy and enhanced motor function.

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Authors and Affiliations

  1. Department of Orthopaedicsa, Dayi Hospital of Shanxi Medical University, Taiyuan, 030032, China

    Hai-Hu Hao & Yi-Jia Jia

  2. Department of Physiology, Shanxi Medical University, Taiyuan, 030001, China

    Li Wang, Jie Wang & Xiao-Yu Li

  3. Department of Orthopaedics, Taiyuan City Centre Hospital, Taiyuan, 030009, China

    Zhi-Jian Guo & Lang Bai

  4. Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China

    Rui-Ping Zhang

  5. Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China

    Wei-Bing Shuang

  6. Department of Orthopaedicsa, Dayi Hospital of Shanxi Medical University, Taiyuan, 030032, China

    Qiang Liu

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  1. Hai-Hu Hao
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  2. Li Wang
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  3. Zhi-Jian Guo
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  4. Lang Bai
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  7. Yi-Jia Jia
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  9. Xiao-Yu Li
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  10. Qiang Liu
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Correspondence to Qiang Liu.

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Hao, HH., Wang, L., Guo, ZJ. et al. Valproic acid reduces autophagy and promotes functional recovery after spinal cord injury in rats. Neurosci. Bull. 29, 484–492 (2013). https://doi.org/10.1007/s12264-013-1355-6

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  • DOI: https://doi.org/10.1007/s12264-013-1355-6

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