From the Department of Anatomy, Cell Biology and Physiological Sciences (S.M.A., M.F., W.A., N.L.) and Department of Neurology (N.L.), Faculty of Medicine, American University of Beirut, PO Box 11-0236, Riad El-Solh, Diana Tamari Sabbagh (DTS) Building, Bldg 130, John Kennedy St, Beirut 1107 2020, Lebanon.
Radiology. 2020 Nov;297(2):407-416. doi: 10.1148/radiol.2020192645. Epub 2020 Aug 18.
Background Despite the wide use of gadolinium-based contrast agents (GBCAs) for enhanced MRI, their neurochemical and behavioral consequences, if any, remain poorly understood. Purpose To investigate the effect of repeated exposure to a linear or macrocyclic GBCA on gadolinium retention in the central and peripheral nervous system of rats and to assess the functional implications of such retention on hippocampal neurogenesis and sensory and cognitive processing. Materials and Methods Seventy male Sprague-Dawley rats (4 weeks old) received intraperitoneal injections of gadoterate meglumine (0.6 or 2.5 mmol per kilogram of body weight), gadodiamide (0.6 or 2.5 mmol/kg), or saline daily for 20 days (February 2018-March 2019). The 5-bromo-2'-deoxyuridine injections were administered every 3 days to determine the number of proliferating cells and the number of newly maturing neurons in the hippocampus. Sensory and cognitive behavioral tests were performed to assess the effect of GBCAs on pain sensitivity and spatial working memory function, respectively. Finally, inductively coupled plasma mass spectrometry analysis was used to quantify gadolinium retention in the brain, spinal cord, and peripheral nerves 24 hours after the last GBCA administration. One-way and mixed-design analyses of variance were used for statistical analysis. Results All GBCAs resulted in significant gadolinium retention in central and peripheral nervous tissues (1.8-333.2 nmol Gd/g tissue). Pain hypersensitivity to thermal and mechanical stimuli ( < .001) was observed after gadodiamide exposure in rats but not after gadoterate meglumine exposure. Rats injected with both GBCAs showed no changes in spatial working memory or in hippocampal cell proliferation and maturation. Conclusion Gadolinium was retained in the spinal cord and peripheral nerves in rats exposed to multiple administrations of linear and macrocyclic contrast agents. Gadodiamide (linear contrast agent) but not gadoterate meglumine (macrocyclic contrast agent) led to pain hypersensitivity, but neither affected spatial working memory performance, hippocampal cellular proliferation, or hippocampal neurogenesis. © RSNA, 2020 See also the editorial by Radbruch in this issue.
背景 尽管钆基对比剂（GBCA）广泛用于增强 MRI，但它们的神经化学和行为后果（如果有的话）仍知之甚少。目的 研究重复暴露于线性或大环 GBCA 对大鼠中枢和周围神经系统中钆保留的影响，并评估这种保留对海马神经发生以及感觉和认知处理的功能影响。材料与方法 70 只雄性 Sprague-Dawley 大鼠（4 周龄）接受腹腔注射钆喷酸葡胺（0.6 或 2.5mmol/kg 体重）、钆双胺（0.6 或 2.5mmol/kg 体重）或生理盐水，每日 1 次，共 20 天（2018 年 2 月至 2019 年 3 月）。每 3 天注射 5-溴-2'-脱氧尿苷以确定海马中增殖细胞和新成熟神经元的数量。进行感觉和认知行为测试，分别评估 GBCA 对痛觉敏感性和空间工作记忆功能的影响。最后，在最后一次 GBCA 给药后 24 小时，使用电感耦合等离子体质谱分析定量脑、脊髓和周围神经中的钆保留量。采用单因素方差分析和混合设计方差分析进行统计学分析。结果 所有 GBCA 均导致中枢和周围神经系统组织中显著的钆保留（1.8-333.2nmol Gd/g 组织）。在大鼠中，暴露于钆双胺后观察到热和机械刺激引起的痛觉过敏（<.001），但暴露于钆喷酸葡胺后未观察到。接受两种 GBCA 注射的大鼠的空间工作记忆或海马细胞增殖和成熟均无变化。结论 经多次线性和大环造影剂给药后，大鼠的脊髓和周围神经中保留了钆。线性造影剂（钆双胺）而非大环造影剂（钆喷酸葡胺）导致痛觉过敏，但均不影响空间工作记忆表现、海马细胞增殖或海马神经发生。 ©2020RSNA 由 Radbruch 本期杂志中的社论可知。
