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

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.

Erythropoietin ameliorates the motor and cognitive function impairments in a rat model of hepatic cirrhosis.

Hepatic encephalopathy (HE) is a serious consequence of hepatic cirrhosis (HC). Previous studies have demonstrated cognitive impairments in both clinical and animal experiments of HC. Some potential therapeutic agents have been used to alleviate the cognitive symptoms in the animal models of HC. In the current study, the possible effect of erythropoietin (ERY) as a potent neuroprotective agent on motor and cognitive impairments induced by HC has been studied. Male Wistar rats (180-200 g) underwent bile duct ligation (BDL) or sham surgery. Administration of ERY (5,000 IU/kg, i.p., daily for three days) was initiated 2 weeks after surgery and lasted for the next 28 days. Open field, rotarod, Morris water maze and passive avoidance learning was used to evaluate the motor and cognitive function of the animals. ANOVA and repeated measures ANOVA were used to analyze the data. p < 0.05 was considered statistically significant. BDL rats had an increased level of hepatic enzymes and bilirubin. Impairment of balance function by BDL was reversed by ERY. Spatial and passive avoidance learning impairments observed in BDL rats were also reversed by chronic administration of ERY. ERY can be offered as a potential neuroprotective agent in the treatment of patients with HC that manifest mental dysfunctions. Though further studies are needed to clarify the exact mechanisms, the neuroprotective properties of ERY against BDL impairments were demonstrated in the current study.