Valproic acid reduces autophagy and promotes functional recovery after spinal cord injury in rats |
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Authors: | Hai-Hu Hao Li Wang Zhi-Jian Guo Lang Bai Rui-Ping Zhang Wei-Bing Shuang Yi-Jia Jia Jie Wang Xiao-Yu Li Qiang Liu |
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Institution: | 11355. Department of Orthopaedicsa, Dayi Hospital of Shanxi Medical University, Taiyuan, 030032, China 21355. Department of Physiology, Shanxi Medical University, Taiyuan, 030001, China 31355. Department of Orthopaedics, Taiyuan City Centre Hospital, Taiyuan, 030009, China 41355. Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China 51355. Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030001, China 61355. Department of Orthopaedicsa, Dayi Hospital of Shanxi Medical University, Taiyuan, 030032, China
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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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Keywords: | spinal cord injury autophagy valproic acid LC3 Beclin-1 |
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