Obstructive jaundice in rats: cause of spatial memory deficits with recovery after biliary decompression

Children with end-stage liver disease have been found to have cognitive deficits. The aim of this study was to examine whether cholestatic jaundice causes spatial deficits in rats and if these cognitive deficits are reversed by biliary drainage. Rats were randomly divided into three groups. In the first group, the bile duct was ligated for 3 weeks (BDL group); in the second group, the proximal bile duct was ligated with a Broviac CV catheter for 2 weeks followed by a tube bilioduodenostomy (TBD group); in the third group, a sham operation was performed (SHAM group). All the surviving rats were assessed for spatial learning and memory (a major cognitive function in rats) by the Morris water maze task about 3 weeks after the first operation. Blood was aspirated by cardiocentesis and assayed for total bilirubin, albumin, ammonia, and hemoglobin levels on the day following the water maze task. During the four consecutive acquisition trial days of the Morris water maze, jaundiced rats (BDL group) had a significant longer latency to escape than the SHAM group (p < 0.05). Rats that underwent biliary decompression for 1 week (TBD group) showed improved status of the spatial deficit, as they required less time to reach the escape platform, approaching the performance of the SHAM group. The BDL group had a significantly higher serum ammonia level, higher bilirubin level, and lower hemoglobin level than the other two groups. After biliary decompression for 1 week, the serum albumin concentration in the TBD group still did not return to the level of the SHAM group. The results of this study suggest that long-term cholestasis results in spatial memory deficits in rats that correlate with anemia and hyperbilirubinemia encephalopathy. Early biliary decompression of obstructive jaundice improves spatial memory deficits, possibly related to the recovery of the serum ammonia and hemoglobin levels.