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.

Free Total Rhubarb Anthraquinones Protect Intestinal Injury via Regulation of the Intestinal Immune Response in a Rat Model of Severe Acute Pancreatitis

“…Evans blue (EB) is closely attached to albumin, so it is used as a common indicator for protein extravasation in inflammatory tissue injury ( Cheng et al, 2016 ). Therefore, we evaluated the intestinal microvascular permeability by EB staining and the ratio of wet-dry weight of intestinal tissues.…”

“…Microvascular permeability and tissue edema are the important pathophysiological characteristics of intestinal dysfunction ( Woodruff et al, 2016 ). Determination of tissue EB which is closely attached to albumin reflects inflammatory tissue injury as a method for the examination of the extent of capillary permeability ( Diao et al, 2012 ; Cheng et al, 2016 ). In addition, the ratio of wet/dry weight is also an important indicator of capillary permeability ( Nakagawa et al, 2009 ).…”

“…After 24 h reaction, 1 ml leachate was taken out and measured at the absorbance 620 nm by a spectrophotometer (Molecular Devices Corporation, Sunnyvale, CA, United States). EB standard curve was established by dilution method (0.15625–80 μg/ml) to calculate the EB content as described previously ( Cheng et al, 2016 ). Rests of the ileum were weighed and placed in an oven at 80°C bake for 72 h for determination of the ratio of wet/dry weight as described previously ( Nakagawa et al, 2009 ).…”

The Neuroimmune Role of Intestinal Microbiota in the Pathogenesis of Cardiovascular Disease

“…Tight junction proteins are important as an element in the intestinal barrier in the structure of the gut–brain axis. It was shown that ghrelin, a brain–gut peptide, attenuates intestinal barrier dysfunction activating tight junction proteins zonula occludens-1 and claudin-5 after intracerebral hemorrhage in animal model [ 70 ]. Some studies demonstrate the relationship of gut microbiome changes with intestinal barrier injury through alteration of tight junction proteins.…”

The relationship between mucosal damage in celiac disease and the risk of neurological and psychiatric conditions is much more complex than previously thought

“…Intestinal biopsies from different groups (celiac patients with active disease, celiac patients in remission, non‐celiac patients with gluten sensitivity and non‐celiac controls) showed a greater increase in permeability when exposed to gliadin in the CD group with active disease and in non‐celiac patients with gluten sensitivity compared with the CD group in remission; in addition, interleukin‐10 (IL‐10) seems to play a significant role in intestinal permeability and IL‐10 deficiency increases permeability before the development of barrier mucosal inflammation . Conversely, ghrelin seems to reduce intestinal barrier damage following intracerebral hemorrhage in mice .…”