Conlee J W, Shapiro S M
University of Utah School of Medicine, Department of Anatomy, Salt Lake City.
Hear Res. 1991 Dec;57(1):23-30. doi: 10.1016/0378-5955(91)90070-p.
Mechanisms underlying bilirubin encephalopathy and hearing loss remain poorly understood, including the way bilirubin enters the nervous system and how bilirubin accumulates in circumscribed regions of the brain. The present experiments examined the auditory brainstem in heterozygous (Nj) and homozygous (jj) Gunn rats at an age when serum bilirubin levels were highest, and after brain bilirubin concentration was artificially raised by sulfadimethoxine administration. In four litters of 11-12 days old Gunn rats, Nj and jj littermates received a single intraperitoneal injection of sulfadimethoxine (100 mg/kg) or a comparable volume of saline. At 16-17 days of age, brainstem auditory evoked potentials were recorded to assess the severity of bilirubin toxicity in the Nj and jj animals. Following the recordings, each animal was perfusion-fixed and frozen sections of the brainstem were cut in the transverse plane from medullary through mesencephalic levels. Sections were mounted on slides, stained with thionin and coded to avoid observer bias. Quantitative analysis revealed no differences between saline and sulfa-treated Nj rats for cochlear nucleus volume, or for cell size in the cochlear nucleus or superior olive. In the sulfa-treated jj rats, cochlear nucleus volume, and cross-sectional areas of spherical cells in the anteroventral cochlear nucleus and principal cells in the nucleus of the trapezoid body, were all significantly smaller than in the combined groups of Nj animals. The affected areas in the cochlear nucleus and superior olive are innervated by large axosomatic end-bulbs of Held or calyceal endings, and were associated with bilirubin staining of glia in the most severely jaundiced jj sulfa-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
胆红素脑病和听力损失的潜在机制仍未得到充分理解，包括胆红素进入神经系统的方式以及胆红素如何在大脑的特定区域积聚。本实验研究了杂合子（Nj）和纯合子（jj）Gunn大鼠在血清胆红素水平最高的年龄阶段，以及在通过磺胺二甲氧嘧啶给药人为提高脑胆红素浓度后的听觉脑干情况。在四窝11 - 12日龄的Gunn大鼠中，Nj和jj同窝幼崽分别接受一次腹腔注射磺胺二甲氧嘧啶（100 mg/kg）或等量的生理盐水。在16 - 17日龄时，记录脑干听觉诱发电位以评估Nj和jj动物中胆红素毒性的严重程度。记录完成后，对每只动物进行灌注固定，并从延髓到中脑水平在横切面上切取脑干的冰冻切片。将切片安装在载玻片上，用硫堇染色并编码以避免观察者偏差。定量分析显示，生理盐水处理组和磺胺处理组的Nj大鼠在耳蜗核体积、耳蜗核或上橄榄核细胞大小方面没有差异。在磺胺处理的jj大鼠中，耳蜗核体积、前腹侧耳蜗核中的球形细胞以及梯形体核中的主细胞的横截面积均显著小于Nj动物的合并组。耳蜗核和上橄榄核中受影响的区域由Held大轴体终球或杯状终末支配，并且在黄疸最严重的磺胺处理jj大鼠中与神经胶质的胆红素染色有关。（摘要截断于250字）
