Analysis of the Gadolinium retention in the Experimental Autoimmune Encephalomyelitis (EAE) murine model of Multiple Sclerosis |
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| Affiliation: | 1. Department of Molecular Biotechnologies and Health Sciences, University of Torino, Via Nizza 52, 10126, Torino, Italy;2. Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Torino, Regione Gonzole 10, 10043, Orbassano, Torino, Italy;3. Neurology Unit, -CReSM (Regional Referring Center of Multiple Sclerosis), AOU San Luigi Gonzaga, Regione Gonzole 10, 10043, Orbassano, Torino, Italy;4. Department of Neuroscience Rita Levi-Montalcini, University of Torino, Via Cherasco 15, 10126, Torino, Italy;1. Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, and Ministry of Education (MOE) Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, PR China;2. Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, Guangdong Province, 518051, PR China;1. Univ. Grenoble Alpes, CEA, IRIG, 38000, Grenoble, France;2. Univ. Grenoble Alpes, INSERM U1055, Laboratory of Fundamental and Applied Bioenergetics (LBFA), and Environmental and System Biology (BEeSy), 38000, Grenoble, France;1. Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, 530021, China;2. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, 530021, China;3. Atmospheric Environment Research Center, Scientific Research Academy of Guangxi Environmental Protection, Nanning, 530022, China;4. Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention, Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China;5. Department of Preventive Medicine, School of Public Health and Management, Guangxi University of Chinese Medicine, Nanning, 530200, China;6. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, United States;1. Department of Physiology, School of Sport Sciences, University of Extremadura, Avenida de la Universidad s/n, 10003 Cáceres, Extremadura, Spain;2. Department of Sport Science, Faculty of Education, Pontifical University of Salamanca, C/Henry Collet, 52–70, CP: 37007 Salamanca, Spain;3. Movement, Brain and Health (MOBhe) Research Group, Center of Higher Education Alberta Giménez, affiliated to Comillas Pontifical University, Costa de Saragossa 16, 07013 Palma, Mallorca, Balearic Islands, Spain;4. Faculty of Language and Education, University of Nebrija, Campus La Berzosa, Calle del Hostal, 28248, Hoyo de Manzanares, Madrid, Spain;1. Center for Advanced Studies and Technology (C.A.S.T.), "G. d''Annunzio" University of Chieti-Pescara, Via Luigi Polacchi 11, Chieti, I-66100, Italy;2. Department of Physics, Università Degli Studi di Milano, Via Celoria 16, Milano, I-20133, Italy;3. LASA, Department of Physics, Università Degli Studi di Milano and INFN-Milano, Via F.lli Cervi 201, Segrate, MI, I-20090, Italy;4. Institute of Clinical Immunotherapy and Advanced Biological Treatments, Piazza Pierangeli 1, Pescara, Rectorate of Leonardo da Vinci Telematic University, Largo San Rocco 11 Torrevecchia Teatina, CH, Italy;5. Department of Medicine and Aging Sciences, "G. d''Annunzio" University of Chieti-Pescara, via Luigi Polacchi 11, Chieti, I-66100, Italy |
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| Abstract: | ObjectivesThe aim of this study is to quantitatively investigate, at the preclinical level, the extent of Gd retention in the CNS, and peripheral organs, of immune-mediated murine models (Experimental Autoimmune Encephalomyelitis –EAE) of Multiple Sclerosis, compared to control animals, upon the injection of gadodiamide. The influence of the Gadolinium Based Contrast Agent administration timing during the course of EAE development is also monitored.MethodsEAE mice were injected with three doses (1.2 mmol/kg each) of gadodiamide at three different time points during the EAE development and sacrificed after 21 or 39 days. Organs were collected and the amount of Gd was quantified through Inductively Coupled Plasma-Mass Spectrometry. Transmission electron microscopy (TEM) and MRI techniques were applied to add spatial and qualitative information to the obtained results.ResultsIn the spinal cord of EAE group, 21 days after gadodiamide administration, a significantly higher accumulation of Gd occurred. Conversely, in the encephalon, a lower amount of Gd retention was reached, even if differences emerged between EAE and controls mice. After 39 days, the amounts of retained Gd markedly decreased. TEM validated the presence of Gd in CNS. MRI of the encephalon at 7.1T did not highlight any hyper intense region.ConclusionIn the spinal cord of EAE mice, which is the mostly damaged region in this specific animal model, a preferential but transient accumulation of Gd is observed. In the encephalon, the Gd retention could be mostly related to inflammation occurring upon immunization rather than to demyelination. |
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| Keywords: | Gadolinium retention Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Gadodiamide Gadolinium based contrast agents |
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