Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats

Language
en
Document Type
Article
Issue Date
2021-02-12
Issue Year
2020
Authors
Habermeyer, Johanna
Boyken, Janina
Harrer, Julia
Canneva, Fabio
Ratz, Veronika
Moceri, Sandra
Admard, Jakob
Casadei, Nicolas
Jost, Gregor
Bäuerle, Tobias
Editor
Abstract

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.

Journal Title
Scientific Reports
Volume
10
Citation

Scientific Reports 10 (2020): 22385. https://www.nature.com/articles/s41598-020-79374-z

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