title: A new hepatic encephalopathy model to monitor the change of neural amino acids and astrocytes with behaviour disorder.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Isobe-Harima
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.forename: Izumi
authors.initials: I
authors.lastname: Miura
authors.forename: Makoto
authors.initials: M
authors.lastname: Segawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Murata
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Itamoto
authors.forename: Yasuho
authors.initials: Y
authors.lastname: Taura
authors.forename: Koh
authors.initials: K
authors.lastname: Shinoda
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D000082:Acetaminophen / Q000633:toxicity; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids; D000082:Acetaminophen; D008748:Methylcholanthrene