Gadolinium Presence in the Brain After Gadolinium-based Contrast Agents: Evidence from Animal Behavioral Studies

Since the discovery of gadolinium (Gd) in the brain following the administration of gadolinium-based contrast agents (GBCAs), considerable progress has been made in understanding their pharmacokinetics and neurotoxicology. This review summarizes animal studies assessing the presence of Gd after GBCA administration, with a specific focus on functional and behavioral outcomes, rather than providing a comprehensive overview of all aspects of Gd presence in the brain. These findings indicate that Gd accumulation in the brain depends on the chemical structure of GBCAs, with linear agents exhibiting greater retention and slower clearance than macrocyclic agents. Gd distribution is nonhomogeneous, primarily localized in deep gray matter structures, and is influenced by cerebrospinal fluid-mediated transport and perivascular deposition. Although motor and cognitive functions are generally unaffected under normal conditions, prolonged exposure to linear GBCAs or preexisting conditions such as inflammation or metabolic disorders may increase neurotoxic risks, resulting in motor and cognitive deficits. Pain and sensory hypersensitivity are frequently and reproducibly observed, particularly when linear agents are used. We will also discuss the potential mechanisms of neurotoxicity caused by free Gd3+ ion. However, these mechanistic findings are limited because the studies cannot be extrapolated to clinical practice. Future studies should investigate the potential associations between GBCA exposure and neurodegenerative diseases. These insights are essential for enhancing GBCA safety and informing clinical guidelines.