Roger C, Koziel V, Vert P, Nehlig A
INSERM U 272, Université de Nancy I, France.
Brain Res Dev Brain Res. 1993 Nov 19;76(1):115-30. doi: 10.1016/0165-3806(93)90129-x.
The clinical features of kernicterus have been extensively described. However, there are still no data available on a possible correlation between the areas which appear to preferentially accumulate bilirubin and regional changes in cerebral functional activity. Therefore, we applied the quantitative autoradiographic [14C]2-deoxyglucose method to the measurement of local cerebral metabolic rates for glucose (LCMRglc) in immature rats receiving a bilirubin infusion. A loading dose of 160 mg/kg bilirubin in a buffered serum albumin solution was first given to the rats over 15 min. Thereafter, bilirubin was infused at a reduced rate, 64 mg/kg/h. Bilirubin infusion lasted from 2 to 3 h according to the age of the animal, in order to obtain a plasma concentration of bilirubin ranging from 200 to 300 mumol/l over the experimental period. Bilirubin entered the brain without any sign of blood-brain barrier alteration. The [14C]2-deoxyglucose was injected to the animals 45 min before the end of bilirubin infusion. Rats were studied at 3 postnatal ages, 10 (P10), 14 (P14) and 21 days (P21). Hyperbilirubinemia induced widespread decreases in LCMRglc's in all brain areas and at all ages. These decreases were mostly prominent in sensory areas, auditory and visual, as well as in hypothalamic and thalamic regions. Especially at P10, the distribution of LCMRglc's was strikingly heterogeneous in both cerebral cortex and caudate nucleus, appearing as alternate dark and white columns or as alternate dark and light dots, respectively. The data of the present study are in agreement with clinical observations reporting that bilirubin mostly accumulates in the striatum and cranial nerves and that the neurological sequelae of kernicterus are very often hearing loss as well as motor problems.
核黄疸的临床特征已得到广泛描述。然而，关于胆红素似乎优先积聚的区域与脑功能活动的区域变化之间可能存在的相关性，目前仍没有相关数据。因此，我们应用定量放射自显影[¹⁴C]2-脱氧葡萄糖法来测量接受胆红素输注的未成熟大鼠的局部脑葡萄糖代谢率（LCMRglc）。首先在15分钟内给大鼠静脉注射160mg/kg胆红素的缓冲血清白蛋白溶液。此后，以64mg/kg/h的速率输注胆红素。根据动物年龄，胆红素输注持续2至3小时，以便在实验期间使血浆胆红素浓度达到200至300μmol/L。胆红素进入大脑，未出现血脑屏障改变的迹象。在胆红素输注结束前45分钟给动物注射[¹⁴C]2-脱氧葡萄糖。对出生后3个年龄段的大鼠进行研究，分别为10日龄（P10）、14日龄（P14）和21日龄（P21）。高胆红素血症在所有年龄段的所有脑区均导致LCMRglc广泛降低。这些降低在感觉区域（听觉和视觉）以及下丘脑和丘脑区域最为明显。特别是在P10时，大脑皮层和尾状核中LCMRglc的分布明显不均匀，分别表现为交替的深色和白色柱状或交替的深色和浅色点状。本研究的数据与临床观察结果一致，临床观察报告称胆红素主要积聚在纹状体和颅神经中，核黄疸的神经后遗症通常是听力丧失以及运动问题。
