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

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 a...

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Autores principales:	Johanna Habermeyer, Janina Boyken, Julia Harrer, Fabio Canneva, Veronika Ratz, Sandra Moceri, Jakob Admard, Nicolas Casadei, Gregor Jost, Tobias Bäuerle, Thomas Frenzel, Christoph Schmitz, Gunnar Schütz, Hubertus Pietsch, Stephan von Hörsten
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/475697f1def341ca8d5a1b8ad2c58eaf
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spelling	oai:doaj.org-article:475697f1def341ca8d5a1b8ad2c58eaf2021-12-02T14:01:28ZComprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats10.1038/s41598-020-79374-z2045-2322https://doaj.org/article/475697f1def341ca8d5a1b8ad2c58eaf2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79374-zhttps://doaj.org/toc/2045-2322Abstract 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.Johanna HabermeyerJanina BoykenJulia HarrerFabio CannevaVeronika RatzSandra MoceriJakob AdmardNicolas CasadeiGregor JostTobias BäuerleThomas FrenzelChristoph SchmitzGunnar SchützHubertus PietschStephan von HörstenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Johanna Habermeyer Janina Boyken Julia Harrer Fabio Canneva Veronika Ratz Sandra Moceri Jakob Admard Nicolas Casadei Gregor Jost Tobias Bäuerle Thomas Frenzel Christoph Schmitz Gunnar Schütz Hubertus Pietsch Stephan von Hörsten Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats
description	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.
format	article
author	Johanna Habermeyer Janina Boyken Julia Harrer Fabio Canneva Veronika Ratz Sandra Moceri Jakob Admard Nicolas Casadei Gregor Jost Tobias Bäuerle Thomas Frenzel Christoph Schmitz Gunnar Schütz Hubertus Pietsch Stephan von Hörsten
author_facet	Johanna Habermeyer Janina Boyken Julia Harrer Fabio Canneva Veronika Ratz Sandra Moceri Jakob Admard Nicolas Casadei Gregor Jost Tobias Bäuerle Thomas Frenzel Christoph Schmitz Gunnar Schütz Hubertus Pietsch Stephan von Hörsten
author_sort	Johanna Habermeyer
title	Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats
title_short	Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats
title_full	Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats
title_fullStr	Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats
title_full_unstemmed	Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats
title_sort	comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/475697f1def341ca8d5a1b8ad2c58eaf
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Comprehensive phenotyping revealed transient startle response reduction and histopathological gadolinium localization to perineuronal nets after gadodiamide administration in rats

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