Valproic Acid: A Potential Therapeutic for Spinal Cord Injury

被引:6
作者
Zhou, Conghui [1 ]
Hu, Songfeng [2 ]
Botchway, Benson O. A. [3 ]
Zhang, Yong [1 ]
Liu, Xuehong [1 ]
机构
[1] Shaoxing Univ, Dept Histol & Embryol, Med Coll, Shaoxing 312000, Zhejiang, Peoples R China
[2] Shaoxing Hosp Tradit Chinese Med, Dept Orthoped, Shaoxing 312000, Zhejiang, Peoples R China
[3] Zhejiang Univ, Sch Med, Inst Neurosci, Hangzhou, Peoples R China
关键词
Valproic acid; mTOR signaling pathway; Inflammation; Autophagy; Spinal cord injury; TRAUMATIC BRAIN-INJURY; PROMOTES FUNCTIONAL RECOVERY; MEDIATED NEUROPROTECTION; TRANSCRIPTOMIC CHANGES; INDUCED INFLAMMATION; AXONAL REGENERATION; NERVE REGENERATION; MOTOR FUNCTION; UP-REGULATION; RAT MODEL;
D O I
10.1007/s10571-020-00929-9
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The lack of an effective pharmaceutical agent for spinal cord injury (SCI) is a current problematic situation for clinicians, as the rate of motor vehicle accidents among young adults is on the rise. SCI contributes to the high disability rate. Presently, evidences detailing the precise pathological mechanisms in SCI are limited, compounding to the unavailability of an effective treatment method. Surgery, though not a complete curative method, is useful in managing some of the associated symptoms of secondary SCI. Autophagy and inflammation are contributive factors to both exacerbation and improvement of SCI. The mammalian target of rapamycin (mTOR) signaling pathway is a key player in the regulation of inflammatory response and autophagy. Valproic acid (VPA), a clinically used antiepileptic drug, has been suggested to improve neurological conditions, including SCI. This report reviewed the correlation between mTOR and autophagy, as well as autophagy's role and the therapeutic effects of VPA in SCI. VPA regulates autophagy by potentially inhibiting mTORC1, a complex of mTOR, while also hindering inflammatory response. Conclusively, an effective treatment for SCI could lie in the timely regulation of mTOR signaling pathway, and VPA could be the potential drug that improves SCI owing to its propensity to regulate the mTOR signaling pathway.
引用
收藏
页码:1441 / 1452
页数:12
相关论文
共 91 条
[1]   Spinal myoclonus complicating spasticity in spinal cord injury: A case study [J].
Andary, MT ;
Green, DF ;
Hulce, VD ;
Pysh, JJ .
ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION, 1997, 78 (09) :1007-1009
[2]   Valproic Acid Is a Novel Activator of AMP-Activated Protein Kinase and Decreases Liver Mass, Hepatic Fat Accumulation, and Serum Glucose in Obese Mice [J].
Avery, Lindsay B. ;
Bumpus, Namandje N. .
MOLECULAR PHARMACOLOGY, 2014, 85 (01) :1-10
[3]   Netrin-1 Improves Functional Recovery through Autophagy Regulation by Activating the AMPK/mTOR Signaling Pathway in Rats with Spinal Cord Injury [J].
Bai, Liangjie ;
Mei, Xifan ;
Shen, Zhaoliang ;
Bi, Yunlong ;
Yuan, Yajiang ;
Guo, Zhanpeng ;
Wang, Hongyu ;
Zhao, Haosen ;
Zhou, Zipeng ;
Wang, Chen ;
Zhu, Kunming ;
Li, Gang ;
Lv, Gang .
SCIENTIFIC REPORTS, 2017, 7
[4]   Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock [J].
Bambakidis, Ted ;
Dekker, Simone E. ;
Sillesen, Martin ;
Liu, Baoling ;
Johnson, Craig N. ;
Jin, Guang ;
de Vries, Helga E. ;
Li, Yongqing ;
Alam, Hasan B. .
JOURNAL OF NEUROTRAUMA, 2016, 33 (16) :1514-1521
[5]   Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF [J].
Bernard, Monique ;
Dieude, Melanie ;
Yang, Bing ;
Hamelin, Katia ;
Underwood, Katy ;
Hebert, Marie-Josee .
AUTOPHAGY, 2014, 10 (12) :2193-2207
[6]   Valproic Acid-Mediated Neuroprotection and Regeneration in Injured Retinal Ganglion Cells [J].
Biermann, Julia ;
Grieshaber, Philippe ;
Goebel, Ulrich ;
Martin, Gottfried ;
Thanos, Solon ;
Di Giovanni, Simone ;
Lagreze, Wolf Alexander .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2010, 51 (01) :526-534
[7]   Clinical and biological changes under treatment with lithium carbonate and valproic acid in sporadic amyotrophic lateral sclerosis [J].
Boll, Marie-Catherine ;
Bayliss, Leo ;
Vargas-Canas, Steven ;
Burgos, Jorge ;
Montes, Sergio ;
Penaloza-Solano, Guillermo ;
Rios, Camilo ;
Alcaraz-Zubeldia, Mireya .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2014, 340 (1-2) :103-108
[8]   Autophagy Is Activated in Injured Neurons and Inhibited by Methylprednisolone After Experimental Spinal Cord Injury [J].
Chen, Hsien-Chih ;
Fong, Tsorng-Harn ;
Lee, Ai-Wei ;
Chiu, Wen-Ta .
SPINE, 2012, 37 (06) :470-475
[9]   Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3 [J].
Chen, Shoubo ;
Ye, Jingfang ;
Chen, Xiangrong ;
Shi, Jinnan ;
Wu, Wenhua ;
Lin, Wenping ;
Lin, Weibin ;
Li, Yasong ;
Fu, Huangde ;
Li, Shun .
JOURNAL OF NEUROINFLAMMATION, 2018, 15
[10]   Valproic acid's effects on visual acuity in retinitis pigmentosa: a systemic review and Meta-analysis [J].
Chen, Wen-Jun ;
Ma, Li ;
Li, Ming-Shu ;
Ma, Xiang .
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY, 2019, 12 (01) :129-134