Low-dose metformin treatment in the subacute phase improves the locomotor function of a mouse model of spinal cord injury  

作　　者：Wen-Ye Song Han Ding Tiffany Dunn Jun-Ling Gao Javier Allende Labastida Caitlin Schlagal Guang-Zhi Ning Shi-Qing Feng Ping Wu 

机构地区：[1]Department of Neuroscience,Cell Biology&Anatomy,University of Texas Medical Branch at Galveston,Galveston,TX,USA [2]Department of Orthopedics,Tianjin Medical University General Hospital,Tianjin,China

出　　处：《Neural Regeneration Research》2021年第11期2234-2242,共9页中国神经再生研究（英文版）

基　　金：supported by a grant from The Institute for Rehabilitation and Research Foundation,No.MC018-112(to PW);John S.Dunn Foundation,No.18168(to PW);the National Natural Science foundation of China,Nos.81620108018(to SQF),81930070(to SQF),82072439(to GZN);Tianjin Key Research and Development Plan,Key Projects For Science and Technology Support of China,No.19YFZCSY00660(to SQF);the National Key R&D Program of China,No.2019YFA0112100(to SQF).

摘　　要：Metformin,a first-line drug for type-2 diabetes,has been shown to improve locomotor recovery after spinal cord injury.However,there are studies reporting no beneficial effect.Recently,we found that high dose of metformin(200 mg/kg,intraperitoneal)and acute phase administration(immediately after injury)led to increased mortality and limited locomotor function recovery.Consequently,we used a lower dose(100 mg/kg,i.p.)metformin in mice,and compared the effect of immediate administration after spinal cord injury(acute phase)with that of administration at 3 days post-injury(subacute phase).Our data showed that metformin treatment starting at the subacute phase significantly improved mouse locomotor function evaluated by Basso Mouse Scale(BMS)scoring.Immunohistochemical studies also revealed significant inhibitions of microglia/macrophage activation and astrogliosis at the lesion site.Furthermore,metformin treatment at the subacute phase reduced neutrophil infiltration.These changes were in parallel with the increased survival rate of spinal neurons in animals treated with metformin.These findings suggest that low-dose metformin treatment for subacute spinal cord injury can effectively improve the functional recovery possibly through anti-inflammation and neuroprotection.This study was approved by the Institute Animal Care and Use Committee at the University of Texas Medical Branch(approval No.1008041C)in 2010.

关 键 词：inflammation locomotor function METFORMIN MICROGLIA mortality NEUROPROTECTION spinal cord injury subacute administration 

分 类 号：R453[医药卫生—治疗学] R744[医药卫生—临床医学]