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Int. J. Mol. Sci. 2016, 17(12), 2032; doi:10.3390/ijms17122032

Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice

1
Department of Neurosurgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
2
Department of Neurology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3
Neuroscience and Neuroengineering Research Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Suzanne L. Dickson
Received: 21 September 2016 / Revised: 10 November 2016 / Accepted: 28 November 2016 / Published: 6 December 2016
(This article belongs to the Special Issue Neurobiological Perspectives on Ghrelin)
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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. View Full-Text
Keywords: intracerebral hemorrhage; ghrelin; intestinal barrier dysfunction; mucosa; intestinal permeability; tight junction; ICAM-1 intracerebral hemorrhage; ghrelin; intestinal barrier dysfunction; mucosa; intestinal permeability; tight junction; ICAM-1
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Cheng, Y.; Wei, Y.; Yang, W.; Cai, Y.; Chen, B.; Yang, G.; Shang, H.; Zhao, W. Ghrelin Attenuates Intestinal Barrier Dysfunction Following Intracerebral Hemorrhage in Mice. Int. J. Mol. Sci. 2016, 17, 2032.

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