PMID: 8938312Feb 1, 1996Paper

Neurotoxic effects of gadopentetate dimeglumine: behavioral disturbance and morphology after intracerebroventricular injection in rats.

AJNR. American Journal of Neuroradiology
D E RayS C Williams

Abstract

To determine the neurotoxic potential of gadopentetate dimeglumine in an animal model that allowed the agent to avoid the blood-brain barrier. Gadopentetate dimeglumine is known to produce functional changes when injected into the cerebrospinal fluid, and we hypothesized that such changes might be associated with morphologic damage. Conscious rats, surgically prepared with a lateral ventricular cannula, were given a slow injection of gadopentetate dimeglumine into the lateral ventricle, and behavioral and neuropathologic changes were noted. Gadopentetate dimeglumine produced signs of acute neurotoxicity over several hours (stereotyped movements and myoclonus), medium-term signs over several days (ataxia and tremor), and neuropathologic changes over 24 hours, with reactive changes persisting for 42 days. All of the above were dose-dependent over the range of 2.5 to 15 mumol/g brain. The lowest dose producing morphologic or behavioral changes was 5 mu mol/g brain. Iso-osmotic, isovolumetric injections of sucrose produced no such effects. Focal lesions occurred within the thalamus, brain stem, and spinal cord, with necrosis of glia, loss of myelin, and, usually, sparing of neurons and nerve fibers. Persisting ataxia was always ass...Continue Reading

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