Effects of Gadolinium Deposits in the Cerebellum: Reviewing the Literature from In Vitro Laboratory Studies to In Vivo Human Investigations
Abstract
:1. Introduction
2. Gadolinium-Based Contrast Agent (GBCA) Deposition in the Cerebellum
3. Effects of GBCAs on Cerebellar Structure and Function
3.1. Human Studies
3.2. Animal Studies
4. Possible Mechanisms of GBCA Toxicity
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
MRI | Magnetic resonance imaging |
GBCA | Gadolinium-based contrast agent |
T1WI | T1-weighted images |
FDA | Food and drug administration |
DN | Dentate nucleus |
DCN | Deep cerebellar nucleus |
GP | Globus pallidus |
ICP-MS | Inductively-coupled plasma mass spectrometry |
Gd | Gadolinium |
Fe | Ferrum |
Zn | Zinc |
Cu | Cuprum |
Gd-DTPA | Gadolinium-diethylenetriaminepentacetate |
Gd-DTPA-BMA | Gadolinium-diethylenetriaminepentacetate-bis-(methylamide) |
Gd-DOTA | Gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid |
ORT | Object recognition test |
OLT | Object-in-location test |
Ca | Calcium |
DIV | Days in vitro |
TH | Thyroid hormone |
TR | Thyroid hormone receptor |
TRE | Thyroid hormone response element |
CaMKIV | Ca2+/calmodulin-dependent protein kinase type IV |
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Investigators | Model of Study | Type of GBCAs | Doses | Durations | Findings |
---|---|---|---|---|---|
Toczylowska et al., 2014 [48] | In Vitro: Primary culture of cerebellar granule cells | Gadobutrol | 0.1, 1 and 10 mM | 30–60 min exposure at DIV7 | Reduction of the toxic effects of indocyanine green by increasing the cell viability of cerebellar granule cells culture 24 h after the exposure. |
Ariyani et al., 2016 [47] | In Vitro: Primary culture of cerebellar Purkinje cells | GdCl3; gadodiamide; gadoterate meglumine | 0.1 and 10 µM | DIV1–DIV17 | Alteration of dendrite arborization and cell number of Purkinje cells by gadodiamide and GdCl3, but not gadoterate meglumine. |
Ray et al., 1996 [38] | In Vivo: Rat | Gadopentetate dimeglumine | 10 µmol/g brain (brain weight estimates at 2 g) | Single intracerebroventricular injection | Morphology: Focal lesions within the thalamus, brain stem, and spinal cord, with necrosis of glia, loss of myelin, and sparing of neurons and nerve fibers, but no description of cerebellar morphology. Behavior: Induction of ataxia with various grades starting at 28–220 min after injection, and lasting for up to 8 days. |
Ray et al., 1998 [37] | In Vivo: Rat | gadodiamide; gadopentetate dimeglumine | 10 µmol/g brain (brain weight estimates at 2 g) | Single intracerebroventricular injection | Morphology: Astrocyte hypertrophy and hyperplasia by gadodiamide, starting from 3 days after the injection. Hypertrophy of Bergmann glia and Purkinje cell Behavior: Incoordination in walking for several hours after gadodiamide injection. Development of ataxia and a high-stepping gait by a higher dose of gadodiamide later than 4 days after injection. Development of ataxia by gadopentetate dimeglumine at 24 h after injection; The symptom being more severe with transient anesthesia. |
Khairinisa et al., 2017 [20] | In Vivo: Mouse | gadodiamide; gadoterate meglumine | 2 mmol/kg body weight per day | day 15 to 19 of pregnancy | Induced of the disrupted motor coordination and impaired memory function by gadodiamide and gadoterate meglumine in adulthood. |
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Khairinisa, M.A.; Ariyani, W.; Tsushima, Y.; Koibuchi, N. Effects of Gadolinium Deposits in the Cerebellum: Reviewing the Literature from In Vitro Laboratory Studies to In Vivo Human Investigations. Int. J. Environ. Res. Public Health 2021, 18, 7214. https://doi.org/10.3390/ijerph18147214
Khairinisa MA, Ariyani W, Tsushima Y, Koibuchi N. Effects of Gadolinium Deposits in the Cerebellum: Reviewing the Literature from In Vitro Laboratory Studies to In Vivo Human Investigations. International Journal of Environmental Research and Public Health. 2021; 18(14):7214. https://doi.org/10.3390/ijerph18147214
Chicago/Turabian StyleKhairinisa, Miski Aghnia, Winda Ariyani, Yoshito Tsushima, and Noriyuki Koibuchi. 2021. "Effects of Gadolinium Deposits in the Cerebellum: Reviewing the Literature from In Vitro Laboratory Studies to In Vivo Human Investigations" International Journal of Environmental Research and Public Health 18, no. 14: 7214. https://doi.org/10.3390/ijerph18147214