Effects of Gadolinium Deposition in the Brain on Motor or Behavioral Function: A Mouse Model
Effects of Gadolinium Deposition in the Brain on Motor or Behavioral Function: A Mouse Model
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DOI：
10.1148/radiol.2021210892
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发表时间：
2021-11-01
期刊：
影响因子：
19.7
通讯作者：
Kiryu, Shigeru
中科院分区：
文献类型：
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作者：
Akai, Hiroyuki;Miyagawa, Kazuya;Kiryu, Shigeru
背景：最近的研究显示钆在多个器官中沉积，这引起了人们对钆基造影剂（gbca）安全性的担忧。目的：探讨钆在脑结构中的沉积是否会引起运动或行为的改变。材料与方法：本研究于2019年7月至2020年12月进行。每组17只雌性BALB/c小鼠重复注射磷酸盐缓冲盐水（对照组，A组）、大环GBCA （B组）或线性GBCA （c组），连续8周（GBCA每周每公斤体重5 mmol）。每隔一周进行脑MRI检查，观察钆沉积引起的信号强度变化。注射期结束后，进行旋转棒性能测试、开放场测试、升高+迷宫测试、光暗焦虑测试、运动活动评估测试、被动回避记忆测试、y型迷宫测试、强迫游泳测试，评估运动能力、焦虑水平和记忆。组间差异比较采用单向或双向因子分析方差与Tukey事后检验或Dunnett事后检验。结果：注射线性GBCA的小鼠，仅MRI证实双侧小脑深部核内钆沉积。8周时，C组的对比比（0.11,95% CI: 0.10, 0.12）高于A组(-2.1 × 10(-3)；95% CI: -0.011, 7.5 × 10(-)(3)；P < 0.001)和B组（2.7 × 10(-)）(4)；95% CI: -8.2 × 10(-3), 8.7 × 10(-3)；P < 0.001)。行为分析显示，注射线性或大环gbca的小鼠的运动能力、焦虑水平和长期或短期记忆没有差异。结论：脑钆沉积对小鼠的运动和行为无明显影响。此外，研究结果支持大环钆基造影剂的安全性。(c) rsna, 2021
Background: Recent studies showing gadolinium deposition in multiple organs have raised concerns about the safety of gadolinium-based contrast agents (GBCAs).Purpose: To explore whether gadolinium deposition in brain structures will cause any motor or behavioral alterations.Materials and Methods: This study was performed from July 2019 to December 2020. Groups of 17 female BALB/c mice were each repeatedly injected with phosphate-buffered saline (control group, group A), a macrocyclic GBCA (group B), or a linear GBCA (group C) for 8 weeks (5 mmol per kilogram of bodyweight per week for GBCAs). Brain MRI studies were performed every other week to observe the signal intensity change caused by the gadolinium deposition. After the injection period, rotarod performance test, open field test, elevated plus-maze test, light-dark anxiety test, locomotor activity assessment test, passive avoidance memory test, Y-maze test, and forced swimming test were performed to assess the locomotor abilities, anxiety level, and memory. Among-group differences were compared by using one-way or two-way factorial analysis of variance with Tukey post hoc testing or Dunnett post hoc testing.Results: Gadolinium deposition in the bilateral deep cerebellar nuclei was confirmed with MRI only in mice injected with a linear GBCA. At 8 weeks, contrast ratio of group C (0.11; 95% CI: 0.10, 0.12) was higher than that of group A (-2.1 x 10(-3); 95% CI: -0.011, 7.5 x 10(-)(3); P < .001) and group B (2.7 x 10(-)(4); 95% CI: -8.2 x 10(-3), 8.7 x 10(-3); P < .001). Behavioral analyses showed that locomotor abilities, anxiety level, and long-term or short-term memory were not different in mice injected with linear or macrocyclic GBCAs.Conclusion: No motor or behavioral alterations were observed in mice with brain gadolinium deposition. Also, the findings support the safety of macrocyclic gadolinium-based contrast agents. (C) RSNA, 2021