Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats

// Mingchu Fang 1 , Huai Jiang 1 , Lixia Ye 1 , Chenchen Cai 1 , Yingying Hu 1 , Shulin Pan 1 , Peijun Li 2 , Jian Xiao 3 and Zhenlang Lin 1 1 Department of Neonatology, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China 2 Center for Neuroscience Research, Children’s National Health System, Washington, DC 20010, United States 3 Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China Correspondence to: Jian Xiao, email: xfxj2000@126.com Zhenlang Lin, email: linzhenlang@hotmail.com Keywords: metformin, neonatal hypoxic-ischemic brain injury, neuronal apoptosis, neuroinflammation, blood-brain barrier Received: June 27, 2017     Accepted: July 30, 2017     Published: September 08, 2017 ABSTRACT Neonatal hypoxic-ischemic (HI) brain injury is a devastating disease that often leads to death and detrimental neurological deficits. The present study was designed to evaluate the ability of metformin to provide neuroprotection in a model of neonatal hypoxic-ischemic brain injury and to study the associated molecular mechanisms behind these protective effects. Here, we found that metformin treatment remarkably attenuated brain infarct volumes and brain edema at 24 h after HI injury, and the neuroprotection of metformin was associated with inhibition of neuronal apoptosis, suppression of the neuroinflammation and amelioration of the blood brain barrier breakdown. Additionally, metformin treatment conferred long-term protective against brain damage at 7 d after HI injury. Our study indicates that metformin treatment protects against neonatal hypoxic-ischemic brain injury and thus has potential as a therapy for this disease.