Shaia Wayne T, Shapiro Steven M, Heller Andrew J, Galiani David L, Sismanis Aristides, Spencer Robert F
Department of Otolaryngology - Head and Neck Surgery, School of Medicine, Medical College of Virginia Campus, Virginia Commonwealth University Health System, Richmond 23298-0599, USA.
Hear Res. 2002 Nov;173(1-2):82-90. doi: 10.1016/s0378-5955(02)00631-7.
Vestibular gaze and postural abnormalities are major sequelae of neonatal hyperbilirubinemia. The sites and cellular effects of bilirubin toxicity in the brainstem vestibular pathway are not easily detected. Since altered intracellular calcium homeostasis may play a role in neuronal cell death, we hypothesized that altered expression of calcium-binding proteins may occur in brainstem vestibular nuclei of the classic animal model of bilirubin neurotoxicity. The expression of the calcium-binding proteins calbindin-D28k and parvalbumin in the brainstem vestibular pathways and cerebellum of homozygous recessive jaundiced (jj) Gunn rats was examined by light microscopy and immunohistochemistry at 18 days postnatally and compared to the findings obtained from age-matched non-jaundiced heterozygous (Nj) littermate controls. Jaundiced animals exhibited decreased parvalbumin immunoreactivity specifically in synaptic inputs to superior, medial, and inferior vestibular nuclei, and to oculomotor and trochlear nuclei, whereas the neurons retained their normal immunoreactivity. Jaundiced animals also demonstrated a decrease in calbindin expression in the lateral vestibular nuclei and a paucity of calbindin-immunoreactive synaptic endings on the somata of Deiters' neurons. The involved regions are related to the control of the vestibulo-ocular and vestibulospinal reflexes. Decreased expression of calcium-binding proteins in brainstem vestibular neurons may relate to the vestibulo-ocular and vestibulospinal dysfunction seen with clinical kernicterus, and may provide a sensitive new way to assess bilirubin toxicity in the vestibular system.
前庭凝视和姿势异常是新生儿高胆红素血症的主要后遗症。胆红素对脑干前庭通路的毒性作用部位和细胞效应不易检测。由于细胞内钙稳态改变可能在神经元细胞死亡中起作用，我们推测在胆红素神经毒性经典动物模型的脑干前庭核中可能会出现钙结合蛋白表达的改变。通过光学显微镜和免疫组织化学方法，检测了纯合隐性黄疸（jj）Gunn大鼠出生后18天时脑干前庭通路和小脑钙结合蛋白钙结合蛋白-D28k和小白蛋白的表达，并与年龄匹配的非黄疸杂合（Nj）同窝对照的结果进行比较。黄疸动物的小白蛋白免疫反应性降低，特别是在前庭上核、内侧核和下核以及动眼神经核和滑车神经核的突触输入中，而神经元保留其正常免疫反应性。黄疸动物的外侧前庭核中钙结合蛋白表达也降低，并且在Deiters神经元胞体上缺乏钙结合蛋白免疫反应性突触终末。所涉及的区域与前庭眼反射和前庭脊髓反射的控制有关。脑干前庭神经元中钙结合蛋白表达降低可能与临床核黄疸所见的前庭眼和前庭脊髓功能障碍有关，并且可能提供一种评估前庭系统中胆红素毒性的敏感新方法。
