Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion

Journal of Neuroinflammation

Guo-Yuan Yang¹  Yongting Wang¹  Zhijun Zhang³  Xiang Gu³  Xiaoyan Chen³  Yang Wang²  Yaning Li³  Guanghui Tang³  Yanqun Liu² 

[1] Department of Neurology, Med-X Research Institute and School of BME, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 1954 Hua-shan Road, Shanghai 200030, China;Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China;Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China

关键词: Metformin;    Ischemic stroke;    Inflammation;    ICAM-1;    Blood-brain barrier;   

Others  :  1150488
DOI  :  10.1186/s12974-014-0177-4

 received in 2014-04-18, accepted in 2014-09-30,  发布年份 2014

【 摘 要 】

Background

Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms.

Methods

Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways.

Results

Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P?P?+ cells, Gr1⁺ cells, MPO activity and BBB permeability were decreased after metformin administration (P?P?P?

Conclusions

Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.

【 授权许可】

   
2014 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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