新生大鼠高胆红素血症及脑病模型的建立与评价

 目的：建立新生SD大鼠高胆红素血症和胆红素脑病模型并评价其效果。方法：将3 日龄 SD新生大鼠按窝系和体重随机均分为7组,分别经腹腔注射生理盐水（Con）以及胆红素6.25 μg/g（T1）、12.5 μg/g（T2）、25 μg/g（T3）、50 μg/g（T4）、100 μg/g（T5）和200 μg/g（T6）,每天2次,共3 d。末次注射12 h后拍照、称重、取材,称量胃内容物重量,计算胃内容物指数和肝/体重比,测定血清总胆红素和游离胆红素浓度,检测脑组织的含水量、胆红素含量和ATP含量,HE和尼氏染色进行形态学检测。结果：随着注射次数和剂量的增加,新生鼠的一般表现逐渐变差,皮肤和黏膜黄染加重,活动次数逐渐减少,体重增长被抑制,T6组出现体重负增长;死亡率逐渐升高,T6 组72 h死亡率接近100%,停止注射后观察1周,T4和T5组死亡率继续升高;与Con和T1组相比,T3~T5组胃内容物重量及其指数显著降低（P<0.05）;T5 组肝/体重比显著升高（P<0.05）;血清总胆红素、游离胆红素和脑组织总胆红素的浓度在T1~T5组逐渐递增;各组大鼠脑组织的含水量没有差异;脑组织ATP含量在T1~T5组先升高后降低,T3组达高峰,与Con 组相比,T4 组和T5 组显著降低(P<0.05)。HE染色结果显示：随着胆红素浓度升高,各组大鼠大脑皮层神经元数量逐渐减少,T4和T5组神经元结构紊乱,细胞肿胀,部分细胞核染色质致密浓缩。尼氏染色显示,随着胆红素浓度增多,神经元胞体逐渐变小,尼氏小体减少、染色逐渐变浅,T4和T5组部分神经元溶解甚至消失。结论：新生3 日龄SD大鼠腹腔注射胆红素12.5、25、50和100 μg/g,每天2次,注射3 d可致高胆红素血症,50和100 μg/g可引起胆红素脑病的发生。     

Neonatal hyperbilirubinemia and kernicterus — Not gone but sometimes forgotten

The introduction of exchange transfusion made it possible to prevent severe hyperbilirubinemia and kernicterus, but kernicterus has never completely disappeared and it is still occurring in North America and, more frequently in Western Europe and the developing world. I discuss the epidemiology and major causes of severe hyperbilirubinemia and the potential root causes and system failures associated with the development of extreme hyperbilirubinemia and, subsequently, kernicterus. In the Western world, kernicterus remains a rare cause of cerebral palsy but, in contrast to the other causes of cerebral palsy, kernicterus should almost always be preventable. The key elements in preventing kernicterus are risk assessment and appropriate follow-up for the newborn infant and these are presented in a recently developed algorithm. Implementation of this approach might contribute to the prevention of severe hyperbilirubinemia and bilirubin encephalopathy.     

Hyperintense globus pallidus on T1-weighted MR imaging in acute kernicterus: is it common or rare?

Globus pallidus involvement is a well-known magnetic resonance (MR) imaging finding of acute kernicterus. However, it is not clear how early the involvement of globus pallidus occurs and whether or not it is seen in every case. Therefore, we aimed to investigate the globus pallidus involvement in 13 neonates with acute kernicterus by MR imaging. Thirteen neonates who were admitted with jaundice, encephalopathy and indirect hyperbilirubinemia (mean, 37.0 mg/dl) were prospectively evaluated with cranial MR imaging. Pathological signal changes were noted concerning the globus pallidus. Eight of the 13 patients demonstrated bilateral, symmetric increased signal intensity in the globus pallidus on T1-weighted MR imaging. These lesions were not apparent on T2-weighted images. Multiple parenchymal punctuate T1 hyperintense lesions were detected in one patient without globus pallidus involvement. This appearance was consistent with hemorrhage. The MR imaging findings of the other four patients showed no evidence of abnormality. The symmetric involvement of globus pallidus seen as hyperintense on T1-weighted MR imaging is a common and characteristic finding of acute kernicterus.     

兴奋性氨基酸受体拮抗剂对胆红素神经毒性细胞内Ca~(2 )的影响

目的　探讨胆红素神经毒性脑组织细胞内 Ca2 变化 ,以及兴奋性氨基酸受体拮抗剂的治疗作用。　方法　在制作胆红素脑病动物模型 (新生 SD鼠 )基础上 ,通过兴奋性氨基酸受体拮抗剂磷酸甲基谷氨酰氨酸 (GAPA) 10 μg/ g干预 ,取脑组织消化、分离、漂洗、制作神经细胞悬液 ,2 -苯丙呋喃基 - 5 -恶唑羧酸五钾 /细胞膜粘合剂负载 ,荧光图像分析测定细胞内 Ca2 荧光强度。　结果　模型组神经细胞内 Ca2 荧光强度 F340 nm/ F380 nm比值为 0 .71± 0 .0 9,显著高于正常对照组的 0 .6 1±0 .0 9;干预组神经细胞内 Ca2 荧光强度 F340 nm/ F380 nm比值为 0 .6 5± 0 .0 8,显著低于模型组。　结论　胆红素神经毒性脑组织细胞内 Ca2 超载 ,兴奋性氨基酸受体拮抗剂 GAPA可拮抗胆红素毒性脑组织细胞内 Ca2 超载。     

胆红素脑病磁共振及磁共振波谱研究进展

胆红素脑病是由于新生儿时期严重的高胆红素血症所致的神经综合征。磁共振与磁共振波谱分别利用原子核在磁场内共振所产生的信号重建成像，和化学位移作用原理测定化合物信号，无创性地研究疾病发生时脑内组织代谢及生理生化改变，为进一步明确胆红素脑病的发病机制和早期准确地评估预后提供了一种手段和方法。本文对它的应用价值及进展作一综述。     

Normal neurological outcome in two infants treated with exchange transfusions born to mothers with Crigler-Najjar Type 1 disorder

Patients with Crigler-Najjar Type 1 (CN-1) disorder have an unconjugated hyperbilirubinaemia due to the complete absence in activity of uridinediphosphate glucuronosyltransferase, a bilirubin-conjugating enzyme. In pregnant women with CN-1, the foetus is at high risk of being adversely affected by the bilirubin, as unconjugated bilirubin can cross the placenta and is potentially neurotoxic. We report the long-term outcomes of two infants born to women with CN-1. These infants had exchange transfusions soon after birth and have normal neurodevelopmental outcomes at 18 months and four years of age, respectively. We propose that this intervention might have improved the neurological outcome of these infants. There are no conflicts of interest reported by any of the authors. Funding was not required.