Intranasal Basic Fibroblast Growth Factor Attenuates Endoplasmic Reticulum Stress and Brain Injury in Neonatal Hypoxic-ischaemic Injury

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2017 Mar 25

PMID 28337259

Citations 7

Authors

Zhenlang Lin

Yingying Hu

Zhouguang Wang

Shulin Pan

Hao Zhang

Libing Ye

Hongyu Zhang

Mingchu Fang

Huai Jiang

Junming Ye

Jian Xiao

Li Liu

Affiliations

Soon will be listed here.

Abstract

Brain injury secondary to birth asphyxia is the major cause of death and long-term disability in newborns. Intranasal drug administration enables agents to bypass the blood-brain barrier (BBB) and enter the brain directly. In this study, we determined whether intranasal basic fibroblast growth factor (bFGF) could exert neuroprotective effects in neonatal rats after hypoxic-ischaemic (HI) brain injury and assessed whether attenuation of endoplasmic reticulum (ER) stress was associated with these neuroprotective effects. Rats were subjected to HI brain injury via unilateral carotid artery ligation followed by 2.5 h of hypoxia and then treated with intranasal bFGF or vehicle immediately after HI injury. We found that the unfolded protein response (UPR) was strongly activated after HI injury and that bFGF significantly reduced the levels of the ER stress signalling proteins GRP78 and PDI. bFGF also decreased brain infarction volumes and conferred long-term neuroprotective effects against brain atrophy and neuron loss after HI brain injury. Taken together, our results suggest that intranasal bFGF provides neuroprotection function partly by inhibiting HI injury-induced ER stress. bFGF may have potential as a therapy for human neonates after birth asphyxia.

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