Inhibition of endoplasmic reticulum stress is involved in the neuroprotective effect of aFGF in neonatal hypoxic-ischaemic brain injury

// Yingying Hu 1, * , Zhouguang Wang 2, * , Shulin Pan 1 , Mingchu Fang 1 , Huai Jiang 1 , Yuqin Mao 2 , Hao Zhang 1 , Yiming Ji 3 , Fabiao Zhang 3 , Li Lin 2 , Zhenlang Lin 1 and Jian Xiao 2 1 Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China 2 Molecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China 3 Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, 317000, China * These authors contributed equally to this work Correspondence to: Li Lin, email: linliwz@hotmail.com Zhenlang Lin, email: linzhenlang@hotmail.com Jian Xiao, email: xfxj2000@126.com Keywords: acidic fibroblast growth factor, neonatal hypoxic-ischaemic brain injury, endoplasmic reticulum stress, intranasal Received: January 23, 2017      Accepted: April 11, 2017      Published: April 29, 2017 ABSTRACT Acidic fibroblast growth factor (aFGF) has been shown to exert neuroprotective effects in experimental models and human patients. In this study, we investigated whether aFGF intranasal-treatment protected against neonatal hypoxic-ischaemic brain injury and evaluated the role of endoplasmic reticulum stress. The Rice-Vannucci model of neonatal hypoxic-ischaemic brain injury was used in 7-day-old rats, which were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia. Intranasal aFGF or vehicle was administered immediately after hypoxic-ischaemic injury (100 ng/g) and then twice a day for 1 week to evaluate the long-term effects. Here we reported that intranasal-treatment with aFGF significantly reduced hypoxic-ischaemic brain infarct volumes and the protective effects were at least partially via inhibiting endoplasmic reticulum stress. In addition, aFGF exerted long-term neuroprotective effects against brain atrophy and neuron loss at 7-day after injury. Our data indicate that therapeutic strategies targeting endoplasmic reticulum stress may be promising to the treatment of neonatal hypoxic-ischaemic brain injury.