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Fulminant liver failure model with hepatic encephalopathy in the mouse.

Hori T, Chen F, Baine AM, Gardner LB, Nguyen JH - Ann Gastroenterol (2011)

Bottom Line: The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without BT care.Between the experimental groups, there were significant differences in aspartate aminotransferase levels and PT-INR; and significant differences in PT-INRs between sufficiently- and insufficiently-hydrated groups.Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).

ABSTRACT

Aim: To develop a reliable murine model for fulminant liver failure (FLF).

Material and methods: We treated three groups of male C57BL/6 mice:as controls, with azoxymethane (AOM), and with galactosamine (Gal) and tumor necrosis factor-alpha (TNFα). Effects of body temperature (BT) control on survival, in all three groups were investigated. Using BT control, survival, histopathological findings and biochemical/coagulation profiles were compared between the experimental groups. Effects of hydration on international normalized ratios of prothrombin time (PT-INR) were also checked. Dose-dependent survival curves were made for both experimental groups. Neurological behaviors were assessed using a coma scale.

Results: No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. Between the experimental groups, there were significant differences in aspartate aminotransferase levels and PT-INR; and significant differences in PT-INRs between sufficiently- and insufficiently-hydrated groups. There were significant differences between FLF models, in the duration of each coma stage, with significant differences in stages 1 and 3 as percentages of the diseased state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study.

Conclusion: Azoxymethane can provide a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

No MeSH data available.


Related in: MedlinePlus

Neurological findings for coma staging in fulminant liver failure (FLF)models. 6To obtain a reliable coma stage, close and/or continuous observation of murine behavior was required. Detailed evaluation about coma status of the mice was performed by the close observation of every 30 min until Stage 2 and the continuous monitor after Stage 2. Note that the continuous observation is crucial for a reliable staging, especially after Stage 2, because the periodic observation never provide an accurate assessment for disease progression and a reliable staging for encephalopathy. A. A mouse at Stage 0 stands straight and runs fast. B. Mouse at Stage 1 walks slow but straight (red arrow). The movement of the feet is slightly impaired (blue arrow). C. At Stage 2, an ataxic finding is enhanced, but any reflexes are kept. The totter is observed (blue arrow), and mouse can not walk straight (red arrow). D. Mouse at Stage 3 is lethargic, and all spontaneous activities are lost. Subsequently, the mouse cannot recover from supine position. E. Eyelash reflex is disturbed at the late phase of Stage 3. F. Mouse becomes unresponsive and grows complacent at Stage 4 (blue arrow).
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Figure 8: Neurological findings for coma staging in fulminant liver failure (FLF)models. 6To obtain a reliable coma stage, close and/or continuous observation of murine behavior was required. Detailed evaluation about coma status of the mice was performed by the close observation of every 30 min until Stage 2 and the continuous monitor after Stage 2. Note that the continuous observation is crucial for a reliable staging, especially after Stage 2, because the periodic observation never provide an accurate assessment for disease progression and a reliable staging for encephalopathy. A. A mouse at Stage 0 stands straight and runs fast. B. Mouse at Stage 1 walks slow but straight (red arrow). The movement of the feet is slightly impaired (blue arrow). C. At Stage 2, an ataxic finding is enhanced, but any reflexes are kept. The totter is observed (blue arrow), and mouse can not walk straight (red arrow). D. Mouse at Stage 3 is lethargic, and all spontaneous activities are lost. Subsequently, the mouse cannot recover from supine position. E. Eyelash reflex is disturbed at the late phase of Stage 3. F. Mouse becomes unresponsive and grows complacent at Stage 4 (blue arrow).

Mentions: The coma scale for mice, which was slightly modified from the previous scale, is summarized in Table 1 [8,23,24]. To obtain a reliable coma stage, close and/or continuous observation of murine behavior was required. Detailed evaluation about coma status of the mice was performed by close observation every 30 min until Stage 2 and continuous monitoring after Stage 2. Important findings for staging were shown in Fig. 8. Note that continuous observation is crucial for reliable staging, especially after Stage 2, because periodic observation never provides an accurate assessment for disease progression and reliable staging for encephalopathy.


Fulminant liver failure model with hepatic encephalopathy in the mouse.

Hori T, Chen F, Baine AM, Gardner LB, Nguyen JH - Ann Gastroenterol (2011)

Neurological findings for coma staging in fulminant liver failure (FLF)models. 6To obtain a reliable coma stage, close and/or continuous observation of murine behavior was required. Detailed evaluation about coma status of the mice was performed by the close observation of every 30 min until Stage 2 and the continuous monitor after Stage 2. Note that the continuous observation is crucial for a reliable staging, especially after Stage 2, because the periodic observation never provide an accurate assessment for disease progression and a reliable staging for encephalopathy. A. A mouse at Stage 0 stands straight and runs fast. B. Mouse at Stage 1 walks slow but straight (red arrow). The movement of the feet is slightly impaired (blue arrow). C. At Stage 2, an ataxic finding is enhanced, but any reflexes are kept. The totter is observed (blue arrow), and mouse can not walk straight (red arrow). D. Mouse at Stage 3 is lethargic, and all spontaneous activities are lost. Subsequently, the mouse cannot recover from supine position. E. Eyelash reflex is disturbed at the late phase of Stage 3. F. Mouse becomes unresponsive and grows complacent at Stage 4 (blue arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3959336&req=5

Figure 8: Neurological findings for coma staging in fulminant liver failure (FLF)models. 6To obtain a reliable coma stage, close and/or continuous observation of murine behavior was required. Detailed evaluation about coma status of the mice was performed by the close observation of every 30 min until Stage 2 and the continuous monitor after Stage 2. Note that the continuous observation is crucial for a reliable staging, especially after Stage 2, because the periodic observation never provide an accurate assessment for disease progression and a reliable staging for encephalopathy. A. A mouse at Stage 0 stands straight and runs fast. B. Mouse at Stage 1 walks slow but straight (red arrow). The movement of the feet is slightly impaired (blue arrow). C. At Stage 2, an ataxic finding is enhanced, but any reflexes are kept. The totter is observed (blue arrow), and mouse can not walk straight (red arrow). D. Mouse at Stage 3 is lethargic, and all spontaneous activities are lost. Subsequently, the mouse cannot recover from supine position. E. Eyelash reflex is disturbed at the late phase of Stage 3. F. Mouse becomes unresponsive and grows complacent at Stage 4 (blue arrow).
Mentions: The coma scale for mice, which was slightly modified from the previous scale, is summarized in Table 1 [8,23,24]. To obtain a reliable coma stage, close and/or continuous observation of murine behavior was required. Detailed evaluation about coma status of the mice was performed by close observation every 30 min until Stage 2 and continuous monitoring after Stage 2. Important findings for staging were shown in Fig. 8. Note that continuous observation is crucial for reliable staging, especially after Stage 2, because periodic observation never provides an accurate assessment for disease progression and reliable staging for encephalopathy.

Bottom Line: The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without BT care.Between the experimental groups, there were significant differences in aspartate aminotransferase levels and PT-INR; and significant differences in PT-INRs between sufficiently- and insufficiently-hydrated groups.Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience, Mayo Clinic in Florida, Jacksonville, FL 32224, USA (Tomohide Hori, Feng Chen, Ann-Marie T. Baine, Lindsay B. Gardner).

ABSTRACT

Aim: To develop a reliable murine model for fulminant liver failure (FLF).

Material and methods: We treated three groups of male C57BL/6 mice:as controls, with azoxymethane (AOM), and with galactosamine (Gal) and tumor necrosis factor-alpha (TNFα). Effects of body temperature (BT) control on survival, in all three groups were investigated. Using BT control, survival, histopathological findings and biochemical/coagulation profiles were compared between the experimental groups. Effects of hydration on international normalized ratios of prothrombin time (PT-INR) were also checked. Dose-dependent survival curves were made for both experimental groups. Neurological behaviors were assessed using a coma scale.

Results: No unexpected BT effects were seen in the control group. The AOM group, but not the Gal+TNFα group, showed significant differences in survival curves between those with and without BT care. Histopathological assessment showed consistent FLF findings in both experimental groups with BT care. Between the experimental groups, there were significant differences in aspartate aminotransferase levels and PT-INR; and significant differences in PT-INRs between sufficiently- and insufficiently-hydrated groups. There were significant differences between FLF models, in the duration of each coma stage, with significant differences in stages 1 and 3 as percentages of the diseased state (stages 1-4). The two FLF models with BT care showed different survival curves in the dose-dependent survival study.

Conclusion: Azoxymethane can provide a good FLF model, but requires a specialized environment and careful BT control. Other FLF models may also be useful, depending on research purpose. Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

No MeSH data available.


Related in: MedlinePlus