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 1ml/kg 15% solution of CCl4 in olive oil four times a week for 4weeks 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: 1st -intact rats and 2nd-rats pretreated with CCl4. 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 14days. Results: In the frst day of food conditioned reflex study it was established that intact rats reached the food in 157±47sec. Contrary, the time of getting to food of CCl4-rats was 2,1times (p<0.05) longer that suggests the less activity and lethargy of these animals. In the next 7days, 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 CCl4. Since the 7th day we have shown a steady acceleration of fnding the food by intact rats. However, there were not registered data about faster food reinforcement in the group of animals that got CCl4 injection. Moreover, in the group of intact rats we have established the decrease in time of fnding the food by 92%(p<0.05) as compared with the frst day of experiment. Such changes were not obvious for the CCl4-group: we did not fnd the signifcant difference between the reaching food of CCl4-rats at the start and at the 14th day of experiment in the T-shaped maze. Thus, we registered that the time of fnding the food in the CCl4 group was 21.4(p<0.001) greater than in the intact group at the 14th 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 CCl4. 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.