A novel newborn rat kernicterus model created by injecting a bilirubin solution into the cisterna magna.
A novel newborn rat kernicterus model created by injecting a bilirubin solution into the cisterna magna.
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通过将胆红素溶液注入小脑延髓池而创建的新型新生大鼠核黄疸模型。
DOI：
10.1371/journal.pone.0096171
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hua Z
中科院分区：
文献类型：
--
作者：
Song S;Hu Y;Gu X;Si F;Hua Z
核黄疸在世界各地仍有发生，但胆红素神经毒性的机制尚不清楚，缺乏有效的治疗策略。为了解决这些问题，人们建立了几种核黄疸（或急性胆红素脑病）动物模型，但这些模型难度大，价格昂贵。因此，本研究通过将未结合胆红素溶液注射到普通新生SD大鼠的小脑延髓池（CM）中来建立一种简单且经济的新型核黄疸模型。出生后第5天，SD大鼠随机分为胆红素组和对照组。然后，将胆红素溶液或ddH 2 O（pH = 8.5）以10 µg/g（体重）注入CM。 对于模型表征，观察神经行为结果，计算死亡率，并在胆红素注射和断奶后记录体重。采用H&E染色、TUNEL、流式细胞术和Western blotting检测海马细胞凋亡。28日龄时，采用Morris水迷宫实验评价大鼠的学习记忆能力。结果表明，经乌司他丁处理的大鼠表现出明显的神经学异常表现，如紧握拳头、角弓反张和扭转痉挛。与对照组相比，治疗组大鼠的体重增长显著降低（P<0.001）。早期和晚期死亡率的玉红蛋白治疗的大鼠都显着高于对照组（P = 0.004和0.017，分别）。 海马神经细胞出现凋亡和坏死。在Morris水迷宫测试中，接受过赤藓糖醇治疗的大鼠表现比对照组差。通过将胆红素注入CM，我们成功地用普通SD大鼠建立了一种新的核黄疸模型，该模型模拟了急性临床表现和慢性后遗症。特别是，CM注射易于进行;因此，可获得用于后续研究的更稳定的模型。
Kernicterus still occurs around the world; however, the mechanism of bilirubin neurotoxicity remains unclear, and effective treatment strategies are lacking. To solve these problems, several kernicterus (or acute bilirubin encephalopathy) animal models have been established, but these models are difficult and expensive. Therefore, the present study was performed to establish a novel kernicterus model that is simple and affordable by injecting unconjugated bilirubin solution into the cisterna magna (CM) of ordinary newborn Sprague-Dawley (SD) rats. On postnatal day 5, SD rat pups were randomly divided into bilirubin and control groups. Then, either bilirubin solution or ddH2O (pH = 8.5) was injected into the CM at 10 µg/g (bodyweight). For model characterization, neurobehavioral outcomes were observed, mortality was calculated, and bodyweight was recorded after bilirubin injection and weaning. Apoptosis in the hippocampus was detected by H&E staining, TUNEL, flow cytometry and Western blotting. When the rats were 28 days old, learning and memory ability were evaluated using the Morris water maze test. The bilirubin-treated rats showed apparently abnormal neurological manifestations, such as clenched fists, opisthotonos and torsion spasms. Bodyweight gain in the bilirubin-treated rats was significantly lower than that in the controls (P<0.001). The early and late mortality of the bilirubin-treated rats were both dramatically higher than those of the controls (P = 0.004 and 0.017, respectively). Apoptosis and necrosis in the hippocampal nerve cells in the bilirubin-treated rats were observed. The bilirubin-treated rats performed worse than the controls on the Morris water maze test. By injecting bilirubin into the CM, we successfully created a new kernicterus model using ordinary SD rats; the model mimics both the acute clinical manifestations and the chronic sequelae. In particular, CM injection is easy to perform; thus, more stable models for follow-up study are available.
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影响因子：
3.7
作者：
Cardoso FL;Kittel A;Veszelka S;Palmela I;Tóth A;Brites D;Deli MA;Brito MA
通讯作者：
Brito MA
DOI：
10.1136/adc.2006.105361
发表时间：
2007-09-01
影响因子：
4.4
作者：
Manning, Donal;Todd, Peter;Plait, Mary Jane
通讯作者：
Plait, Mary Jane
影响因子：
3.8
作者：
Hemsley, Kim M.;King, Barbara;Hopwood, John J.
通讯作者：
Hopwood, John J.
影响因子：
4.8
作者：
Nguyen, Nghia;Bonzo, Jessica A.;Tukey, Robert H.
通讯作者：
Tukey, Robert H.
DOI：
10.1073/pnas.0913290107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Fujiwara, Ryoichi;Nguyen, Nghia;Tukey, Robert H.
通讯作者：
Tukey, Robert H.