BILIRUBIN TOXICITY IN THE AUDITORY SYSTEM

胆红素脑病是胆红素对肝脏的毒性作用， 大脑，导致脑损伤和耳聋。 发病机制及 胆红素中听觉神经系统功能障碍的部位 脑病仍然是未知和有争议的， 几十年的研究。 脑干听觉诱发电位（BAEPs）， 将对古恩大鼠进行组织学和生物化学测定 胆红素脑病模型，以确定听觉 功能障碍，其时间进程，与发展的相互作用， 可逆性的潜力。 该项目将使用BAEP评估神经生理学变化 急性暴露于胆红素中毒后不久发生。 BAEP 研究结果将与游离和蛋白质的测量结果进行比较， 结合血胆红素，然后到组织学检查结果。 关系 不同年龄的人将研究 未成熟中枢神经系统胆红素毒性。 旨在降低胆红素毒性的干预措施将探索 病理过程可逆性的时间限制。 在相关的研究中，该项目将本地化的具体网站（S） 胆红素引起听觉神经系统功能障碍。 BAEP和 将比较组织学以验证耳蜗的状态， 听觉脑干核团。 调查结果还将涉及 先前描述的生物化学研究。 由此产生的多学科方法预计将提供 对这种疾病的发病机制及其影响的新见解 对听觉系统的影响 和理解复杂的 电生理学、解剖学和 生物化学过程应该会改善非侵入性 用于预测的程序（例如BAEP和血液测试） 人类新生儿的神经和耳科后遗症。

Bilirubin encephalopathy, the result of bilirubin toxicity to the brain, causes brain damage and deafness. The pathogenesis and site(s) of auditory nervous system dysfunction in bilirubin encephalopathy are still unknown and controversial despite decades of study. Brainstem auditory evoked potentials (BAEPs), histology, and biochemical assays will be applied to the Gunn rat model of bilirubin encephalopathy to define the site(s) of auditory dysfunction, its time course, interaction with development, and potential for reversibility. The project will use BAEPs to assess neurophysiological changes occurring soon after acute exposure to bilirubin toxicity. BAEP findings will be compared to measurements of free and protein- bound blood bilirubin, and then to histological findings. Studies at different ages will examine the increased vulnerability of the immature central nervous system to bilirubin toxicity. Interventions aimed at decreasing bilirubin toxicity will explore the time constraints of reversibility of the pathological process. In related studies, the project will localize the specific site(s) of bilirubin induced auditory nervous system dysfunction. BAEPs and histology will be compared to verify the status of the cochlea and the auditory brainstem nuclei. The findings will also be related to the previously described biochemical studies. The resulting multidisciplinary approach is expected to provide new insights into the pathogenesis of this disorder and its effects on the auditory system. And understanding of the complex relationships between electrophysiological, anatomical and biochemical processes should lead to improved noninvasive procedures (e.g. BAEPs and blood tests) for predicting neurological and otological sequelae in human newborns.