Changes in the brain monoamine metabolism in acute liver failure produced by ischemia-reperfusion injury in rats

Objective: To investigate the relationship between behavioral alterations and changes in monoaminergic systems provoked by ischemia-reperfusion liver injury in rats. Design: Prospective, randomized, controlled animal study. Setting: University animal laboratory. Subjects: Male Wistar rats. Interventions: Acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 mins, Twenty animals were subjected to the behavioral examination. The brain water content was measured in 12 animals. Forty-two animals were used for the evaluation of brain monoamine turnover. Half of animals in each experiment were subjected to the ischemic operation. Measurements and Main Results: A step-through passive avoidance test was used for the behavioral evaluation 48 hrs after the ischemic operation, Then, plasma concentrations of amino acids were determined. The brain water content was measured with the dry weight method. The brain monoamine turnover was evaluated by the depletion of norepinephrine and dopamine induced by a methyl-p-tyrosine, or the accumulation of 5-hydroxyindoleacetic acid induced by probenecid. In the plasma analysis performed 48 hrs after the operation, marked damage was found in animals subjected to liver ischemia, injured rats demonstrated impairment in the passive avoidance test, The plasma concentrations of branch-chain amino acids were decreased, and the plasma concentrations of aromatic amino acids were increased. However, the brain water content was not changed by liver ischemia. The turnover of both norepinephrine in the cerebral cortex and dopamine in the striatum was decreased, The turnover of 5-hydroxytryptamine in the cerebral cortex was in creased markedly. Conclusion: In liver injury caused by liver ischemia, the excitatory neurotransmission by norepinephrine and dopamine is depressed and the inhibitory neurotransmission mediated by 5 hydroxytryptamine is facilitated, especially in the telencephalon.