Evaluation of prepulse inhibition and memory impairments at early stage of cirrhosis may be considered as a diagnostic index for minimal hepatic encephalopathy

Abstract

Minimal hepatic encephalopathy (MHE), which represents the early stage of this condition, is not clinically apparent and is prevalent in up to 80% of patients. The poor outcomes of MHE encouraged us to identify more simple methods for early diagnosis of MHE. To this purpose, we evaluated the contemporary manifestations of motor, cognitive and sensorimotor gaiting deficits following bile duct-ligation (BDL). Male Wistar rats were undergone BDL to induce cirrhosis and locomotor, spatial learning and memory and sensorimotor gating were assessed 2, 3, and 4weeks after the operation by rotarod, Morris water-maze and prepulse inhibition (PPI) tests. PPI was examined 6weeks after BDL until appearance of hepatic encephalopathy. Results showed that although PPI was significantly enhanced in the 6-week BDL animals, locomotor activity reduced in 4-week BDL rats compared to the BDL rats after a 2-week period. The total distance travelled and swimming time to reach the platform increased in the 4-week BDL rats and, in contrast, the percentage of time spent and space travelled in correct quadrant decreased. Moreover, memory index decreased in the 3-week BDL group compared to sham-operated group. It was observed an increase in global PPI in 3- and 4-week BDL animals in comparison with either 2-week BDL or sham-operated rats. Consequently, it is indicated that BDL animals manifest spatial learning and memory deficits and PPI disruption in early stage of HE and evaluation of these factors can be considered as indices for simple and early diagnosis of MHE.