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A new hepatic encephalopathy model to monitor the change of neural amino acids and astrocytes with behaviour disorder
Author(s) -
IsobeHarima Yumiko,
Terai Shuji,
Miura Izumi,
Segawa Makoto,
Murata Tomoaki,
Itamoto Kazuhito,
Taura Yasuho,
Shinoda Koh,
Sakaida Isao
Publication year - 2008
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2007.01589.x
Subject(s) - glutamate receptor , acetaminophen , glial fibrillary acidic protein , medicine , glutamine , amino acid , endocrinology , hepatic encephalopathy , glutamine synthetase , astrocyte , centrilobular necrosis , chemistry , biochemistry , necrosis , immunohistochemistry , central nervous system , cirrhosis , receptor
Background/Aims: To elucidate the pathogenesis of hepatic encephalopathy (HE), we developed a new HE model with behaviour disorder. Methods: Male Wistar rats were divided into four treatment groups: a HE model: acetaminophen (APAP)+3‐methylcholanthrene (3‐MC) group (APAP+MC group); control group: acetaminophen group; 3‐methylcholanthrene group; and a no‐treatment group. We monitored the changes of neural amino acids in the synaptic cleft and astrocytes in the brain during behaviour disorder. Results: In the APAP+MC group, alanine amino transferase, blood ammonia and glucose increased from 3 h and total bilirubin increased at 6 h. Prothrombin time was prolonged from 3 h in the APAP+MC group. The APAP+MC group exhibited centrilobular necrosis in the liver after 8 h. In the APAP+MC group, rats jumped vertically and this vertical activity increased significantly from 4 to 7 h. During the behaviour disorder, we found that glutamate and aspartate increased in the synaptic cleft from 4 h after treatment with APAP+3‐MC, glutamate increased 23.9‐fold at 7 h and aspartate increased 16.1‐fold at 4 h, whereas glutamine did not change. At that time, we observed morphological changes of the astrocytes by immunostaining for the glial fibrillary acidic protein. Conclusions: Our new HE model demonstrated that increased excitatory neural amino acids and morphological change in astrocytes were involved in the behaviour disorder that occurs with HE.