Department of Experimental Therapy, University Hospital Erlangen and Preclinical Experimental Animal Center (PETZ), Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Universitätsklinikum Erlangen (UKEr), Palmsanlage 5, 91054, Erlangen, Germany.
Bayer AG, MR & CT Contrast Media Research, Muellerstrasse 178, 13353, Berlin, Germany.
Sci Rep. 2020 Dec 28;10(1):22385. doi: 10.1038/s41598-020-79374-z.
Gadolinium based contrast agents (GBCAs) are widely used in clinical MRI since the mid-1980s. Recently, concerns have been raised that trace amounts of Gadolinium (Gd), detected in brains even long time after GBCA application, may cause yet unrecognized clinical consequences. We therefore assessed the behavioral phenotype, neuro-histopathology, and Gd localization after repeated administration of linear (gadodiamide) or macrocyclic (gadobutrol) GBCA in rats. While most behavioral tests revealed no difference between treatment groups, we observed a transient and reversible decrease of the startle reflex after gadodiamide application. Residual Gd in the lateral cerebellar nucleus was neither associated with a general gene expression pathway deregulation nor with neuronal cell loss, but in gadodiamide-treated rats Gd was associated with the perineuronal net protein aggrecan and segregated to high molecular weight fractions. Our behavioral finding together with Gd distribution and speciation support a substance class difference for Gd presence in the brain after GBCA application.
自 20 世纪 80 年代中期以来，钆基对比剂（GBCA）在临床 MRI 中得到了广泛应用。最近，人们担心在 GBCA 应用后很长时间，即使在大脑中检测到痕量的钆（Gd），也可能会引起尚未被认识到的临床后果。因此，我们评估了在大鼠中重复给予线性（钆喷酸葡胺）或大环（钆布醇）GBCA 后，行为表型、神经组织病理学和 Gd 定位的情况。虽然大多数行为测试未显示治疗组之间存在差异，但我们观察到在给予钆喷酸葡胺后，惊吓反射出现短暂且可逆的下降。外侧小脑核中的残留 Gd 既与一般基因表达途径的失调无关，也与神经元细胞丢失无关，但在给予钆喷酸葡胺的大鼠中，Gd 与神经周细胞网蛋白聚糖有关，并分离到高分子量部分。我们的行为学发现，以及 Gd 的分布和形态，支持 GBCA 应用后大脑中 Gd 存在的物质类别差异。
