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Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation

Anja Geerts (UGent) , Eline Vanheule (UGent) , Marleen Praet (UGent) , Hans Van Vlierberghe (UGent) , Martine De Vos (UGent) and Isabelle Colle (UGent)
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Abstract
The characterization of mice models of portal hypertension (PHT) is lacking in the literature. Therefore, the aim of the present study was to make a histological approach during development of PHT in two models of cirrhosis with PHT compared with one model of isolated PHT. The model of isolated PHT was developed by partial portal vein ligation (PPVL). Two portal hypertensive cirrhotic mice models were developed either by common bile duct ligation (CBDL) or administration of carbon tetrachloride (CCl4) subcutaneously (twice weekly, 1 ml/kg). These models represent, respectively, a secondary biliary cirrhosis and alcoholic cirrhosis. Mice were killed at several time points to evaluate liver changes by histological and ultrastructural methods. A correlation was made with portal pressure measurements. Histology revealed the absence of fibrosis or cirrhosis in PPVL mice. They developed an isolated portal hypertension. After CBDL induction, the mice developed the characteristics of cirrhosis after 6 weeks, with simultaneous increase in portal pressures. Fifty percent of the mice had ascites at that time point. Sixteen weeks after administration of CCl4, a micronodular cirrhotic aspect of the liver was seen associated with signs of portal hypertension. This is the first descriptive study of three widely used animal models in mice, allowing the study of pathophysiological changes in cirrhosis and portal hypertension. The PPVL in mice leads to a model of isolated portal hypertension. Secondary biliary cirrhosis developed after 6 weeks of common bile duct ligation in 50% of the mice that developed ascites. Subcutaneous injection of CCl4 for 16 weeks induces cirrhosis and poral hypertension, without ascites. Moreover, the present study is the first description of a cirrhotic model in mice developed by subcutaneous injections of CCl4. Well-described mice models will facilitate use of knock-out or transgenic mice and lead to a better understanding of the underlying molecular pathways in the field of portal hypertension and cirrhosis.
Keywords
CARBON-TETRACHLORIDE, BILE-DUCT OBSTRUCTION, HEMODYNAMIC CHARACTERIZATION, HYPERDYNAMIC CIRCULATION, ANESTHETIZED RATS, LIGATED RATS, IN-VIVO, CIRRHOSIS, LIVER, ALCOHOL, portal hypertension, partial portal vein ligation, mice models, cirrhosis, carbon tetrachloride, bile duct ligation

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MLA
Geerts, Anja, Eline Vanheule, Marleen Praet, et al. “Comparison of Three Research Models of Portal Hypertension in Mice: Macroscopic, Histological and Portal Pressure Evaluation.” INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY 89.4 (2008): 251–263. Print.
APA
Geerts, Anja, Vanheule, E., Praet, M., Van Vlierberghe, H., De Vos, M., & Colle, I. (2008). Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 89(4), 251–263.
Chicago author-date
Geerts, Anja, Eline Vanheule, Marleen Praet, Hans Van Vlierberghe, Martine De Vos, and Isabelle Colle. 2008. “Comparison of Three Research Models of Portal Hypertension in Mice: Macroscopic, Histological and Portal Pressure Evaluation.” International Journal of Experimental Pathology 89 (4): 251–263.
Chicago author-date (all authors)
Geerts, Anja, Eline Vanheule, Marleen Praet, Hans Van Vlierberghe, Martine De Vos, and Isabelle Colle. 2008. “Comparison of Three Research Models of Portal Hypertension in Mice: Macroscopic, Histological and Portal Pressure Evaluation.” International Journal of Experimental Pathology 89 (4): 251–263.
Vancouver
1.
Geerts A, Vanheule E, Praet M, Van Vlierberghe H, De Vos M, Colle I. Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation. INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY. 2008;89(4):251–63.
IEEE
[1]
A. Geerts, E. Vanheule, M. Praet, H. Van Vlierberghe, M. De Vos, and I. Colle, “Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation,” INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, vol. 89, no. 4, pp. 251–263, 2008.
@article{431821,
  abstract     = {The characterization of mice models of portal hypertension (PHT) is lacking in the literature. Therefore, the aim of the present study was to make a histological approach during development of PHT in two models of cirrhosis with PHT compared with one model of isolated PHT. The model of isolated PHT was developed by partial portal vein ligation (PPVL). Two portal hypertensive cirrhotic mice models were developed either by common bile duct ligation (CBDL) or administration of carbon tetrachloride (CCl4) subcutaneously (twice weekly, 1 ml/kg). These models represent, respectively, a secondary biliary cirrhosis and alcoholic cirrhosis. Mice were killed at several time points to evaluate liver changes by histological and ultrastructural methods. A correlation was made with portal pressure measurements. Histology revealed the absence of fibrosis or cirrhosis in PPVL mice. They developed an isolated portal hypertension. After CBDL induction, the mice developed the characteristics of cirrhosis after 6 weeks, with simultaneous increase in portal pressures. Fifty percent of the mice had ascites at that time point. Sixteen weeks after administration of CCl4, a micronodular cirrhotic aspect of the liver was seen associated with signs of portal hypertension. This is the first descriptive study of three widely used animal models in mice, allowing the study of pathophysiological changes in cirrhosis and portal hypertension. The PPVL in mice leads to a model of isolated portal hypertension. Secondary biliary cirrhosis developed after 6 weeks of common bile duct ligation in 50% of the mice that developed ascites. Subcutaneous injection of CCl4 for 16 weeks induces cirrhosis and poral hypertension, without ascites. Moreover, the present study is the first description of a cirrhotic model in mice developed by subcutaneous injections of CCl4. Well-described mice models will facilitate use of knock-out or transgenic mice and lead to a better understanding of the underlying molecular pathways in the field of portal hypertension and cirrhosis.},
  author       = {Geerts, Anja and Vanheule, Eline and Praet, Marleen and Van Vlierberghe, Hans and De Vos, Martine and Colle, Isabelle},
  issn         = {0959-9673},
  journal      = {INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY},
  keywords     = {CARBON-TETRACHLORIDE,BILE-DUCT OBSTRUCTION,HEMODYNAMIC CHARACTERIZATION,HYPERDYNAMIC CIRCULATION,ANESTHETIZED RATS,LIGATED RATS,IN-VIVO,CIRRHOSIS,LIVER,ALCOHOL,portal hypertension,partial portal vein ligation,mice models,cirrhosis,carbon tetrachloride,bile duct ligation},
  language     = {eng},
  number       = {4},
  pages        = {251--263},
  title        = {Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation},
  url          = {http://dx.doi.org/10.1111/j.1365-2613.2008.00597.x},
  volume       = {89},
  year         = {2008},
}

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