Dissimilar Aluminum and Gallium Permeation of the Blood‐Brain Barrier Demonstrated by In Vivo Microdialysis

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Abstract
Aluminum (Al) and gallium (Ga) permeations of the blood-brain barrier (BBB) were assessed in rats. Unbound extracellular Al and Ga concentrations were ascertained at the two potential sites of BBB permeation, cerebral capillaries and choroid plexuses, by implantation of microdialysis probes in the frontal cortex and lateral ventricle, respectively. A microdialysis probe implanted in the jugular vein revealed unbound blood Al or Ga concentrations. Al or 67Ga citrate was administered via the femoral vein. Peak Al and Ga concentrations were seen within the first 10 min at all three sites. Area under the curve (concentration vs. time to final sample) values were calculated using RSTRIP. Within-rat overall frontal cortical/blood and lateral ventricular/blood ratios [brain/blood ratios (oBBRs)] were calculated from area under the curve values. Aluminum frontal cortical oBBRs were significantly higher than those for the lateral ventricle. Ga oBBRs were not significantly different between the two sites. Al and Ga oBBRs were significantly different in the lateral ventricle. These results suggest that the primary site of Al permeation across the BBB is at cerebral capillaries, whereas Ga permeation across the BBB does not significantly differ between cerebral capillaries and choroid plexuses. The use of Ga as a model to study Al pharmacokinetics may not be appropriate in the elucidation of the site or mechanism of Al entry into the brain.