title: Metformin preconditioning provide neuroprotection through enhancement of autophagy and suppression of inflammation and apoptosis after spinal cord injury.
abstract: Spinal cord injury (SCI) is one of the most serious nervous system disorders characterised by high morbidity and disability. Inflammatory and autophagy responses play an important role in the development of SCI. Metformin, a first-line drug for type-2 diabetes, features autophagy promotion as well as anti-inflammatory and anti-apoptotic properties in the nervous system. In this study, we investigated the neuroprotection effects of metformin preconditioning on rats after SCI. Results of Basso, Beattie and Bresnahan scores, HE staining and Nissl staining showed that the function and quantity of motor neurons were protected by metformin after SCI. Western blot revealed that the expression of Beclin-1 and LC3B-II was enhanced, and the phosphorylation levels of the mammalian target of rapamycin (mTOR) protein and p70S6K were reduced by metformin after SCI. Metformin significantly reduced the expression of NF-κB. Moreover, Western blot and immunofluorescence results indicated that caspase 3 activation was reduced, whereas bcl-2 level was significantly increased by metformin. Hence, metformin attenuated SCI by inhibiting apoptosis and inflammation and enhancing the autophagy via the mTOR/p70S6K signalling pathway.
authors.affiliation: Department of Orthopedic, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. Electronic address: ad2wsx@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China. Electronic address: liuchang1971mei@163.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Jining NO.1 People's Hospital, Jining City, China. Electronic address: gaohaikai88@126.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: Department of Orthopedic, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Haosen
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Orthopedic, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, Second Hospital of Jinzhou, Jinzhou, China.
authors.forename: Zhaoliang
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Orthopedic, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Second Hospital of Jinzhou, Jinzhou, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopedic, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
authors.forename: Tianchen
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Orthopedic, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. Electronic address: meixifan1971@163.com.
authors.forename: Xifan
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D005260:Female; D007249:Inflammation / Q000150:complications / Q000517:prevention & control*; D008687:Metformin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D008687:Metformin; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases
keywords: Apoptosis; Autophagy; Inflammation; Metformin; Spinal cord injury