Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice

• Published in: International journal of molecular sciences 2016-12, Vol.17 (12), p.2032-2032
• Main Authors: Cheng, Yijun, Wei, Yongxu, Yang, Wenlei, Cai, Yu, Chen, Bin, Yang, Guoyuan, Shang, Hanbing, Zhao, Weiguo
• Format: Article
• Language: English
• Subjects: Animals; Cerebral Hemorrhage - blood; Cerebral Hemorrhage - drug therapy; Endotoxins - blood; Ghrelin; Hemorrhage; ICAM-1; Ileum - drug effects; Ileum - metabolism; Intestinal Absorption - drug effects; intestinal barrier dysfunction; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; intestinal permeability; Intestines - drug effects; Intestines - metabolism; intracerebral hemorrhage; Male; Medical prognosis; Mice; Mice, Inbred C57BL; mucosa; Peptides; Rodents; tight junction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms17122032

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.