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

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 firs t group, the acute effects of intrathecal GdD on cortical electroencephalog raphic activity, renal sympathetic nerve activity, arterial blood pressure, and heart rate were determined. In the second group, histological evaluati on of the neural tissues was performed 10 days after treatment. In both the physiological and histological studies, a single GdD dose of 2.5 mu mol/g brain (10 muL) was administered intrathecally, Control animals were injecte d intrathecally with the same volume of a sucrose solution that had the sam e 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 st udy, examination revealed two cases of pre-existing chronic spinal cord gli osis; one of these rats also exhibited signs of pre-existing chronic choroi d plexus inflammation. No acute or subacute alterations observed could be s pecifically linked to the intrathecal administration of GdD, CONCLUSIONS. Intrathecally administered GdD was accompanied by no significa nt change in any of the physiologic or histologic parameters examined. Base d on the relatively short time interval between GdD treatment and histologi c examination, the neural tissue abnormalities (gliosis/inflammation) obser ved in two animals were judged to be incidental and likely due to prior chr onic pre-existing processes such as viral infection. Although additional st udies are required to verify the safety and effectiveness of intrathecal Gd D in humans, data from the present study in animals provide evidence that w hen intrathecal GdD is used in doses sufficient to improve MRI of the cereb rospinal fluid compartment, it is likely to be accompanied by a low inciden ce of acute changes in neural function or structure.