The Changes Of Brainstem Auditory Evoked Potentials And The Mechanisms Of Bilirubin Neurotoxicity In Hyperbilirubinemia Rats

Objective:Brainstem auditory evoked potentials (BAEP) , and the content of nitric oxide (NO) and the activity of Na~+-K~+ATPase of the brain tissues in hyperbilirubinemia rat pups had been observed to explore the significance of BAEP in monitoring the bilirubin-induced brain injury, and the action of NO in the pathogenesis of this disorder, and provide the experimental basis for the early diagnosis and treatment of bilirubin-induced brain injury.Methods:Sixty Sprague-Dewley rats at age of 15-16 day were randomly divided into control group (C, n=10) and five test groups (T1, T2, T3, T4 and T5, n1=10, n2=10, n3=10, n4=10 and n5=10). Bilirubin solutions were injected into the abdominal cavity of the rats of group Tl (30mg/kg), T2 (60mg/kg), T3 (90mg/kg), T4 (120mg/kg) and T5 (150mg/kg), and 1ml physiological saline was injected in the rats of group C. After the injection of 6 hours later, the neuronal behaviors, BAEP, bilirubin concentration of serum and the brain tissues, and the content of NO and the activity of Na~+-K~+ATPase of the brain tissues were examined.Results:1. After the injection 6 hours later, the rats in group T1, T2 and T3 had normal behaviors and were sensitive to the external stimuli, and the rats in group T4 and T5 had abnormal behaviors and were not sensitive to the external stimuli.2. After the injection 6 hours later in the rats of group T2, T3, T4 and T5, bilirubin concentrations of serum and the brain tissues, and the content of NO of the brain tissues increased significantly, but the activity of Na~+-K~+ATPase of the brain tissues decreased obviously (P<0.05 or P<0.01). There was no correlation between the bilirubin concentration of serum and that of the brain tissues ( P>0.05). There was negative correlation between the bilirubin concentration andthe activity of Na+-K+ATPase in the brain tissues (P<0.01), and there was positive correlation between the bilirubin concentration and the NO content in the brain tissues (i><0.01).3. After the injection 6 hours later, the PL of wave III and I ~ III I PL of BAEPin the rats of group T2 prolonged significantly, and the PL of wave I , II and III, and I — III IPL of BAEP in the rats of group T3, T4 and T5 prolonged significantly (P<0.01). There was no correlation between the serum bilirubin concentration and the PL and IPL of BAEP (P>0.05). There was positive correlation between the bilirubin concentration of the brain tissues and the PL and IPL of BAEP (P<0.05 or P<0.0l).Conclusion:l.The hyperbilirubinemia rats can be induced via injection of bilirubin solution into the abdominal cavity of the rat pups.2.There were abnormal changes of BAEP in the hyperbilirubinemia rats, which were positively correlated to the bilirubin concentration of the brain tissues. BAEP is the objective and sensitive index for monitoring the bilirubin-induced brain injury, and has important significance in early detection and objective evaluation of bilirubin-induced brain injury in clinics.3.Bilirubin had strong inhibition effect on the activity of Na+-K+ATPase in the brain tissues, and resulted in generation of a large amount of NO in the brain tissues in hyperbilirubinemia. The increased NO may involve in the pathogenesis of bilirubin-induced brain injury.