Acute and subacute physiological and histological studies of the central nervous system after intrathecal gadolinium injection in the anesthetized rat

Abstract

Rationale and objectives: To determine the acute physiological and subacute neurohistological effects of gadopentetate dimeglumine (GdD) administered intrathecally.

Methods: Twenty-four rats were separated into two study groups. In the first group, the acute effects of intrathecal GdD on cortical electroencephalographic activity, renal sympathetic nerve activity, arterial blood pressure, and heart rate were determined. In the second group, histological evaluation of the neural tissues was performed 10 days after treatment. In both the physiological and histological studies, a single GdD dose of 2.5 micromol/g brain (10 microL) was administered intrathecally. Control animals were injected intrathecally with the same volume of a sucrose solution that had the same osmolality as GdD.

Results: In the physiological study, GdD and sucrose injections elicited no significant change in any of the parameters recorded. In the histologic study, examination revealed two cases of pre-existing chronic spinal cord gliosis; one of these rats also exhibited signs of pre-existing chronic choroid plexus inflammation. No acute or subacute alterations observed could be specifically linked to the intrathecal administration of GdD.

Conclusions: Intrathecally administered GdD was accompanied by no significant change in any of the physiologic or histologic parameters examined. Based on the relatively short time interval between GdD treatment and histologic examination, the neural tissue abnormalities (gliosis/inflammation) observed in two animals were judged to be incidental and likely due to prior chronic pre-existing processes such as viral infection. Although additional studies are required to verify the safety and effectiveness of intrathecal GdD in humans, data from the present study in animals provide evidence that when intrathecal GdD is used in doses sufficient to improve MRI of the cerebrospinal fluid compartment, it is likely to be accompanied by a low incidence of acute changes in neural function or structure.