BILIRUBIN TOXICITY IN THE AUDITORY SYSTEM

人类新生儿仍有脑损伤和听力损失的风险 胆红素毒性尽管在护理和治疗方面取得了进展 高胆红素血症。目前胆红素脑病的范围很广。 从早产儿、低出生体重婴儿的经典核心黄蜂到更多 细微情况或听力损失和认知障碍的孤立后遗症 功能障碍。胆红素中毒所致损害的发生率， 特别是在微妙或孤立的条件下，基本上是未知的 因为很难将生命后期出现的异常现象联系起来 发生在新生儿期的一过性生化异常。 此外，对听神经的发病机制、部位定位进行了探讨。 系统功能障碍，以及脆弱性和 尽管几十年来人们对可逆性仍只有部分了解 学习。 在我们成功使用脑干听觉诱发的基础上 Gunn大鼠胆红素脑病模型的BAEP 将无创神经生理记录与量化相结合 神经解剖研究，生化测量，以及 免疫组织化学提供了一个内聚合成的定位， 胆红素毒性功能障碍的可逆性及发病机制 以及它与发育过程的相互作用。 急性接触后不久出现的电生理学表现 胆红素毒性将与解剖和生化指标进行比较。 旨在逆转急性胆红素中毒的干预措施将用于 探讨病理过程可逆性的时间限制。 在发育早期的不同年龄的研究将检验 未成熟听觉和中枢不同区域的易损性 神经系统对胆红素的毒性。我们将继续努力 胆红素诱发听觉神经系统的特定部位定位(S) 脑干听觉诱发电位功能障碍、耳声发射、双耳交互作用 诱发电位和后潜伏期诱发电位评估损伤 耳蜗和中枢听觉神经系统，并验证我们的 解剖和生化实验的电生理学结果。 由此产生的多学科方法预计将提供新的 对该病的定位、发病机制和可逆性的见解 紊乱，以及它对听觉系统的影响。了解 电生理学、解剖学和生物力学之间的复杂关系 胆红素脑病动物模型的生化过程 导致改进非侵入性程序以预测、预防和 胆红素中毒的神经系统和听力学后遗症的治疗 在人类新生儿身上。

Human newborns are still at risk for brain damaged and hearing loss from bilirubin toxicity despite advances in the care and treatment of hyperbilirubinemia. The spectrum of bilirubin encephalopathy today ranges from classic kernicterus in premature, low-birth-weight infants, to more subtle conditions or the isolated sequelae of hearing loss and cognitive dysfunction. The incidence of impairment due to bilirubin toxicity, especially in the subtle or isolated conditions, is largely unknown because it is difficult to relate abnormalities that appear later in life to transient biochemical abnormalities that occur in the newborn period. Furthermore, the pathogenesis, localization of sites of auditory nervous system dysfunction, and the determinants of vulnerability and reversibility are still only partially understood 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 combine noninvasive neurophysiological recordings with quantitative neuroanatomical studies, biochemical measurements, and immunohistochemistry to provide a cohesive synthesis of the localization, reversibility and pathogenesis of dysfunction due to bilirubin toxicity and its interaction with developmental processes. Electrophysiologic findings that occur soon after acute exposure to bilirubin toxicity will be compared to anatomic and biochemical measures. Interventions aimed at reversing acute bilirubin toxicity will be used to explore the time constraints of reversibility of the pathological process. Studies at different ages early in development will examine the vulnerability of different areas of the immature auditory and central nervous systems to bilirubin toxicity. We will continue our efforts to localize the specific site(s) of bilirubin-induced auditory nervous system dysfunction utilizing BAEPs, otoacoustic emissions, binaural interaction evoked potentials, and later-latency evoked potentials to assess damage to the cochlea and the central auditory nervous system, and verify our electrophysiologic results with anatomic and biochemical experiments. The resulting multidisciplinary approach is expected to provide new insights into the localization, pathogenesis, and reversibility of this disorder, and its effects on the auditory system. Understanding the complex relationships between electrophysiological, anatomical and biochemical processes in animal models of bilirubin encephalopathy should lead to improved noninvasive procedures for predicting, preventing, and treating the neurological and audiological sequelae of bilirubin toxicity in human newborns.