Introduction: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, a major complication of liver disease. The prevalence of the development of cirrhosis is similar in both males and females. The use of animal models of chronic liver disease contributes greatly to the understanding of the mechanisms of HE. To date, fundamental and pre-clinical research in HE has not been investigated in female animals. Since behavioral tests used to assess HE in rats are influenced by the female’s reproductive cycle (the estrous cycle), the aims of this pilot project are 1) to evaluate the estrous cycle, 2) assess degree of liver failure and 3) investigate the neuro phenotype of female bile duct ligated (BDL) rats, (a model of HE) compared to female SHAMs. Methods and results: 6 weeks bile duct ligated (BDL) female rats (N=6) had an increase in body weight, food intake and lean mass (a trend for lower fat mass (p=0.066)), with impaired liver function (p=0.009), dysregulated estrous cycle (measured by daily vaginal cytology), and impaired short-term memory (p=0.057) vs SHAM operated controls (N=4). Historical data from male BDLs showed similar liver and memory impairment, but a decrease in the body weight and food intake vs male SHAMs. Compared to male BDL, female BDL rats showed a similar degree of liver disease as well as short-term memory impairment, which was evident in the diestrous phase. However, a higher increase in body weight and food intake was found in female vs male BDL. A dysregulated estrous cycle was found in female BDL, however, all 4 phases of the cycle were completed. Discussion: These preliminary results demonstrate that there are potential differences between both male and female BDL rats and thus merit to be addressed.
