title: Valproic acid reduces autophagy and promotes functional recovery after spinal cord injury in rats.
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.
authors.affiliation: Department of Orthopaedicsa, Dayi Hospital of Shanxi Medical University, Taiyuan 030032, China.
authors.forename: Hai-Hu
authors.initials: HH
authors.lastname: Hao
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Guo
authors.forename: Lang
authors.initials: L
authors.lastname: Bai
authors.forename: Rui-Ping
authors.initials: RP
authors.lastname: Zhang
authors.forename: Wei-Bing
authors.initials: WB
authors.lastname: Shuang
authors.forename: Yi-Jia
authors.initials: YJ
authors.lastname: Jia
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000473:pathology*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D018696:Neuroprotective Agents; D014635:Valproic Acid; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat