A new hepatic encephalopathy model to monitor the change of neural amino acids and astrocytes with behaviour disorder.
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.
Isobe-Harima
Yumiko
Y
Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Terai
Shuji
S
Miura
Izumi
I
Segawa
Makoto
M
Murata
Tomoaki
T
Itamoto
Kazuhito
K
Taura
Yasuho
Y
Shinoda
Koh
K
Sakaida
Isao
I
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
D000596:Amino Acids; D000082:Acetaminophen; D008748:Methylcholanthrene