title: Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice.
abstract: Intestinal barrier dysfunction remains a critical problem in patients with intracerebral hemorrhage (ICH) and is associated with poor prognosis. Ghrelin, a brain-gut peptide, has been shown to exert protection in animal models of gastrointestinal injury. However, the effect of ghrelin on intestinal barrier dysfunction post-ICH and its possible underlying mechanisms are still unknown. This study was designed to investigate whether ghrelin administration attenuates intestinal barrier dysfunction in experimental ICH using an intrastriatal autologous blood infusion mouse model. Our data showed that treatment with ghrelin markedly attenuated intestinal mucosal injury at both histomorphometric and ultrastructural levels post-ICH. Ghrelin reduced ICH-induced intestinal permeability according to fluorescein isothiocyanate conjugated-dextran (FITC-D) and Evans blue extravasation assays. Concomitantly, the intestinal tight junction-related protein markers, Zonula occludens-1 (ZO-1) and claudin-5 were upregulated by ghrelin post-ICH. Additionally, ghrelin reduced intestinal intercellular adhesion molecule-1 (ICAM-1) expression at the mRNA and protein levels following ICH. Furthermore, ghrelin suppressed the translocation of intestinal endotoxin post-ICH. These changes were accompanied by improved survival rates and an attenuation of body weight loss post-ICH. In conclusion, our results suggest that ghrelin reduced intestinal barrier dysfunction, thereby reducing mortality and weight loss, indicating that ghrelin is a potential therapeutic agent in ICH-induced intestinal barrier dysfunction therapy.
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. jesny1988@163.com.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. weiyongxu@icloud.com.
authors.forename: Yongxu
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. yangwenlei@hotmail.com.
authors.forename: Wenlei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. caiyu10746@sina.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. chenbinns@sjtu.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. yangguoyuan_neuro@163.com.|Neuroscience and Neuroengineering Research Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China. yangguoyuan_neuro@163.com.
authors.forename: Guoyuan
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. hjshb@126.com.
authors.forename: Hanbing
authors.initials: H
authors.lastname: Shang
authors.affiliation: Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. zwg_neurosurgery@yahoo.com.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002543:Cerebral Hemorrhage / Q000097:blood / Q000188:drug therapy*; D004731:Endotoxins / Q000097:blood; D054439:Ghrelin; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D004731:Endotoxins; D054439:Ghrelin
keywords: ICAM-1; ghrelin; intestinal barrier dysfunction; intestinal permeability; intracerebral hemorrhage; mucosa; tight junction