title: Insulin-like growth factor-1 secreted by brain microvascular endothelial cells attenuates neuron injury upon ischemia.
abstract: Insulin-like growth factor (IGF)-1 is essential for the development of the nervous system, and is present in many cell types. Relatively little is known about IGF-1 expression in brain microvascular endothelial cells (BMECs). For in vivo studies, we examined the expression of IGF-1 and insulin-like growth factor-binding protein (IGFBP)-2 after focal cerebral ischemia for 12 h, 24 h, 3 days and 7 days, utilizing a permanent middle cerebral artery occlusion (MCAO) model in rats. For in vitro studies, we examined the levels of IGF-1 and IGFBP-2 in the culture medium or primary culture of BMECs injured by oxygen-glucose deprivation (OGD). Then, we elucidated the protective effects of IGF-1 on cortical neurons injured by OGD and the possible mechanism. In addition, we investigated the effect of BMEC-conditioned medium on IGF-1 receptor expression in neurons. The results showed that IGF-1 expression increased in serum and brain tissue, whereas IGFBP-2 expression decreased in brain tissue of MCAO-injured rats. In primary culture of BMECs, the expression levels of IGF-1 and IGFBP-2 were significantly higher under OGD conditions in culture. IGF-1 administration improved neuron viability upon normoxia or OGD, and upregulated p-Akt expression. This effect was reversed by LY294002, a specific inhibitor of the phosphoinositide 3-kinase-Akt signaling pathway. Furthermore, conditioned medium from OGD-treated BMECs substantially suppressed neuron viability and the expression of IGF-1 receptor simultaneously. These data demonstrate that therapeutic strategies that prioritize the early recovery of the IGF-1 system in BMECs might be promising in ischemic injury.
authors.affiliation: Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yibo
authors.initials: Y
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhao
authors.forename: Runjun
authors.initials: R
authors.lastname: Wang
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Yan
authors.forename: Liwei
authors.initials: L
authors.lastname: Xu
authors.forename: Pengtao
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000098:blood supply; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000502:physiology; D008297:Male; D055806:Microvessels / Q000473:pathology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D018971:Insulin-Like Growth Factor Binding Protein 2; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: brain microvascular endothelial cells; insulin-like growth factor-1 (IGF-1); ischemia; neuron