The Effect of Perinatal Gadolinium-Based Contrast Agents on Adult Mice Behavior

Abstract

In the present study, we showed that Gd was transferred to pups and was retained in their brain during postnatal development. Gadolinium retention may lead to impaired brain development. These findings indicate that the use of GBCAs in pregnant women should be avoided because it may have adverse effects on the fetus, particularly on brain development.

The Effects of Gadolinium-Based Contrast Agents on the Cerebellum: from Basic Research to Neurological Practice and from Pregnancy to Adulthood

“…Motor coordination examined by rotarod was significantly disrupted (Fig. 1b), whereas memory functions examined by object recognition and object-in-location were also disrupted [8]. These behavioral alterations indicate that GBCAs affect the development of several brain regions such as the cerebellum and hippocampus.…”

“…Although the Gd toxicity on cerebellar development and function has not been demonstrated yet, recent studies have provided novel information [8,12]. One such information is that Gd may disrupt the action of thyroid hormone (TH), which plays a critical role on cerebellar development [13].…”

“…Indeed, in recent studies using pregnant mice, Gd was deposited in the brain of dams and pups with higher concentration in the pup brain after GBCA injection [8,9]. Higher levels of Gd deposition in the fetal brain may be due to the immaturity of the blood-brain barrier [10] and the bloodcerebrospinal fluid barrier, both of which are not fully developed in the perinatal period [6,11].…”

“…It may disrupt calcium signaling by blocking Ca 2+ channel which then affects Ca 2+ /calmodulin-dependent protein kinase type IV (CaMKIV)-mediated augmentation of TR action [14] or bind to integrin αVβ3 that is known as TH-binding site [15]. On the other hand, another in vivo study, when gadoterate meglumine or gadodiamide was intravenously injected into dams during perinatal period (embryonic day 15-19, single injection/day), which is the critical period for the functional organization of neuronal circuits, both GBCAs disrupted motor coordination and impaired memory function [8]. The magnitude of disruption was higher with gadodiamide.…”

Dechelation (Transmetalation)

“…Perinatal exposure to a GBCA in mice has been shown to induce behavioral changes, more severe with a linear as opposed to a macrocyclic agent. 76 Although attention has been primarily directed toward the potential for clinical symptoms due to deposition in critical brain nuclei, such as the dentate nucleus, the potential for symptoms due to bone, skin, and liver deposition also exists. In a single case report, previously discussed, in a patient with normal renal function who received a very high number of injections of predominantly linear gadolinium chelates, skin samples demonstrated a very high level of gadolinium deposition, similar to reported levels seen in patients with renal failure and NSF.…”