BILIRUBIN TOXICITY IN THE AUDITORY SYSTEM

尽管在高胆红素血症的护理和治疗方面取得了进展， 新生儿仍然有脑损伤和听力损失的风险， 胆红素毒性 胆红素脑病的临床表现 今天的新生儿从“经典核黄疸”，仍然见于早产儿， 低出生体重儿，更微妙的后遗症孤立听力损失 和认知功能障碍。 胆红素所致损害的发生率 毒性，特别是在后者，更微妙的条件下，在很大程度上是 未知，因为很难将后来出现的异常联系起来 新生儿出现短暂的生化异常 期 此外，听觉神经系统部位的名称 胆红素脑病的功能障碍仍然是未知的和有争议的 尽管经过几十年的研究。 在我们成功使用脑干听觉诱发电位的延续中， 在胆红素脑病的古恩大鼠模型中， 将扩展我们的努力，以确定听觉功能障碍的时间过程， 其可逆性的潜力，以及与发展的相互作用， 流程. 这些努力将包括BAEP与 未结合神经毒素的定量组织学和生物化学测定 胆红素。 旨在降低胆红素毒性的干预措施，如交换 输注白蛋白将胆红素从脑内排出 组织，将探讨可逆性的时间限制， 病理过程。 急性暴露后不久出现的BAEP结果 胆红素毒性将与游离胆红素和蛋白质的测量结果进行比较， 结合血胆红素和组织学结果。 研究表明， 不同年龄的人会发现， 中枢神经系统胆红素毒性。 在相关研究中，我们将 继续努力定位特定部位， 听觉神经系统功能障碍的BAEP和组织学评估 对耳蜗和听觉脑干核团的损害。 由此产生的多学科方法预计将提供新的 深入了解这种疾病的发病机制和可逆性， 对听觉系统的影响 对复合体的理解 电生理、解剖和生化之间的关系 胆红素脑病动物模型的过程应导致 用于预测神经系统疾病的改进的非侵入性程序， 人类新生儿的听力后遗症。

Despite advances in the care and treatment of hyperbilirubinemia, human newborns are still at risk from brain damage and hearing loss from bilirubin toxicity. The spectrum of bilirubin encephalopathy in human newborns today ranges from "classic kernicterus", still seen in premature, low-birth-weight infants, to more subtle sequelae of isolated hearing loss and cognitive dysfunction. The incidence of impairment due to bilirubin toxicity, especially in the latter, more subtle conditions, is largely unknown because it is difficult to relate abnormalities that show up later in life to transient biochemical abnormalities that occur in the newborn period. Furthermore, the name of the sites of auditory nervous system dysfunction in bilirubin encephalopathy are still unknown and controversial despite decades of study. In a continuation of our successful use of brainstem auditory evoked potentials (BAEPs) in the Gunn rat model of bilirubin encephalopathy, we will extend our efforts to define the time course of auditory dysfunction, the potential for its reversibility, and interaction with developmental processes. These efforts will include comparison of BAEPs with quantitative histology and biochemical assays of unbound neurotoxic bilirubin. Intervention aimed at decreasing bilirubin toxicity, such as exchange transfusion and injection of albumin to transfer bilirubin out of brain tissue, will explore the time constraints of reversibility of the pathological process. BAEP findings occurring soon after acute exposure to bilirubin toxicity will be compared to measurements of free and proteins- bound blood bilirubin, and to histological findings. Studies it rats at different ages will examine the increased vulnerability of the immature central nervous system to bilirubin toxicity. In related studies, we will continue our efforts to localize the specific site(s) of bilirubin-induced auditory nervous system dysfunction utilizing BAEPs and histology assess damage to the cochlea and the auditory brainstem nuclei. The resulting multidisciplinary approach is expected to provide new insights into the pathogenesis of and reversibility of this disorder, and its effects on the auditory system. The understanding of the complex relationship between electrophysiological, anatomical and biochemical processes in animal models of bilirubin encephalopathy should lead to improved noninvasive procedures for predicting neurological and audiological sequelae in human newborns.