Mouse intragastric infusion (iG) model

ArticleinNature Protocol 7(4):771-81 · April 2012with25 Reads
DOI: 10.1038/nprot.2012.014 · Source: PubMed
Direct intragastric delivery of a diet, nutrient or test substance can be achieved in rodents (mice and rats) on a long-term (2-3 months) basis using a chronically implanted gastrostomy catheter and a flow-through swivel system. This rodent intragastric infusion (iG) model has broad applications in research on food intake, gastrointestinal (GI) physiology, GI neuroendocrinology, drug metabolism and toxicity, obesity and liver disease. It achieves maximal control over the rate and pattern of delivery and it can be combined with normal ad libitum feeding of solid diet if so desired. It may be adopted to achieve infusion at other sites of the GI system to test the role of a bypassed GI segment in neuroendocrine physiology, and its use in genetic mouse models facilitates the genetic analysis of a central question under investigation.
    • "Under physiological conditions, HSCs store Vitamin A and function as liver pericytes, but in response to sustained exposure to alcohol, HSCs rapidly differentiate into fibrogenic myofibroblasts , start producing Collagen Type I, the major component of extracellular matrix, and make liver fibrotic. To date, the intragastric model of ethanol feeding (Tsukamoto–French model) [12] is the best rodent model of alcohol-induced liver fibrosis, which mimics this stage of alcoholic fibrosis in patients, and these mice develop significant level of liver fibrosis after 2 months of alcohol [12, 13 @BULLET@BULLET ]. This stage is characterized by release of TGF-b1, mostly by Kupffer cells [4], and activation of Hepatic stellate cells (HSCs) [13 @BULLET@BULLET , 14]. "
    [Show abstract] [Hide abstract] ABSTRACT: Alcoholic liver disease (ALD) progresses from a normal liver, to steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). Despite intensive studies, the pathogenesis of ALD is poorly understood, in part due to a lack of suitable animal models which mimic the stages of ALD progression. Furthermore, the role of IL-17 in ALD has not been evaluated. We and others have recently demonstrated that IL-17 signaling plays a critical role in the development of liver fibrosis and cancer. Here we summarize the most recent evidence supporting the role of IL-17 in ALD. As a result of a collaborative effort of Drs. Karin, Gao, Tsukamoto, and Kisseleva, we developed several improved models of ALD in mice: (1) chronic-plus-binge model that mimics early stages of steatohepatitis, (2) intragastric ethanol feeding model that mimics alcoholic steatohepatitis and fibrosis, and (3) diethylnitrosamine (DEN) + alcohol model that mimics alcoholic liver cancer. These models might provide new insights into the mechanism of IL-17 signaling in ALD and help identify novel therapeutic targets.
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    • "Lastly, we found that high fat diet (HCFD) present during Hybrid EtOH+Binge exposure aggravated the increase in P2X7R expression and activation status of astroglia. The iG ethanol exposure model in rodents was recently developed to aid in the investigation of the ethanol-induced liver damage (Tsukamoto et al., 2008; Ueno et al., 2012). Additional studies have reported a synergistic relationship between ethanol exposure and moderate adiposity such as found in the Hybrid paradigm in regards to causing liver damage (Deng et al., 2005; Xu et al., 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: The present investigation tested the role of ATP-activated P2X7 receptors (P2X7Rs) in alcohol-induced brain damage using a model that combines intragastric (iG) ethanol feeding and high fat diet in C57BL/6J mice (Hybrid). The Hybrid paradigm caused increased levels of pro-inflammatory markers, changes in microglia and astrocytes, reduced levels of neuronal marker NeuN and increased P2X7R expression in ethanol-sensitive brain regions. Observed changes in P2X7R and NeuN expression were more pronounced in Hybrid paradigm with inclusion of additional weekly binges. In addition, high fat diet during Hybrid exposure aggravated the increase in P2X7R expression and activation of glial cells. Copyright © 2015 Elsevier B.V. All rights reserved.
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    • "Various animal models have been developed to characterize pathological changes of ALD. In particular, two protocols have been developed in mice that mimic aspects of ALD development in humans: the Lieber-DeCarli alcohol liquid diet [11,12] and the Tsukamoto-French intragastric alcohol feeding protocol [13,14]. Animals on the Lieber-DeCarli liquid diet display significant liver lesions including steatosis, apoptosis, structural alteration of mitochondria and endoplasmic reticulum and corresponding changes like those found early in human ALD. "
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