Improvement of the Modeling and Diagnosis of Hepatic Encephalopathy in Rats

Abstract

Introduction: Modeling of liver cirrhosis (LC) and hepatic encephalopathy (HE) in rats has some limitations namely high mortality of lab animals or high duration of LC formation. Diagnosis of HE was accomplished with the model of food conditioned reflex that allowed evaluating only locomotors activity of animals but not their ability to think and remember. Aims & Methods:That is why the aim of the study was the optimization of the HE modeling and diagnosis. Intra-peritoneal administration of 1 ml/kg 15% solution of CCl 4 in olive oil four times a week for 4 weeks has been suggested for optimal simulation of HE in rats. The development of HE, namely the ability of animals to memorization, learning and thinking was studied by the formation of a food conditioned reflex in the T-shaped maze. 14 rats were divided into two groups: 1 st -intact rats and 2 nd -rats pretreated with CCl 4 . The dynamic of reducing the time of getting animals to the food reinforcement in the maze as a result of remembering the location of food was estimated during 14 days. Results:In the first day of food conditioned reflex study it was established that intact rats reached the food in 157±47 sec. Contrary, the time of getting to food of CCl 4 -rats was 2,1 times (p<0.05) longer that suggests the less activity and lethargy of these animals. In the next 7 days, there were not any changes in the time of getting to food in T-shape maze in the intact group as well as in the group pretreated with CCl 4 . Since the 7 th day we have shown a steady acceleration of finding the food by intact rats. However, there were not registered data about faster food reinforcement in the group of animals that got CCl 4 injection. Moreover, in the group of intact rats we have established the decrease in time of finding the food by 92% (p<0.05) as compared with the first day of experiment. Such changes were not obvious for the CCl 4 -group: we did not find the significant difference between the reaching food of CCl 4 -rats at the start and at the 14 th day of experiment in the T-shaped maze. Thus, we registered that the time of finding the food in the CCl 4 group was 21.4 (p<0.001) greater than in the intact group at the 14 th day of study in the T-shaped maze. The impairment of food conditioned reflex formation has showed lack of remembering and thinking in rats pretreated with CCl 4 . Conclusion:we have updated the scheme of modeling LC and HE by the decrease of time of the LC development and the reduction of animal mortality as result of toxic action by CCl 4 . The improved diagnosis of HE was achieved by using the methodology of forming a food conditioned reflex in rats. This method can be recommended as a basic for HE modeling and can be used for study new treatment strategies of this disease.