Intranasal basic fibroblast growth factor attenuates endoplasmic reticulum stress and brain injury in neonatal hypoxic-ischaemic injury.
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.
Department of Neonatology, The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710061, Shaanxi, China; Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical UniversityWenzhou 325027, Zhejiang, China.
Zhenlang
Z
Lin
Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325027, Zhejiang, China.
Yingying
Y
Hu
Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
Zhouguang
Z
Wang
Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325027, Zhejiang, China.
Shulin
S
Pan
Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325027, Zhejiang, China.
Hao
H
Zhang
Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
Libing
L
Ye
Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
Hongyu
H
Zhang
Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325027, Zhejiang, China.
Mingchu
M
Fang
Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University Wenzhou 325027, Zhejiang, China.
Huai
H
Jiang
Department of Anesthesia, The First Affiliated Hospital, Gannan Medical College Ganzhou, 341000, China.
Junming
J
Ye
Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University Wenzhou 325035, Zhejiang, China.
Jian
J
Xiao
Department of Neonatology, The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061, Shaanxi, China.
Li
L
Liu
ER stress; bFGF; hypoxic-ischaemia brain injury; neuroprotection