Homogeneity of regional brain lead concentrations

It has been proposed that the neurobiological basis of many of the behavioral manifestations arising in response to Pb exposure may be due to selective vulnerability of particular brain regions, such as hippocampus, a region in which preferential accumulation has been reported in some studies. However, these findings have not been invariant and, in fact, have been found to vary with dosing parameters. This study examined potential regional accumulation of Pb in brain following postnatal exposure of rats to Pb via nursing dams consuming Pb acetate solutions of 0, 100, 350, 1000, or 2000 ppm. Offspring were sacrificed at 7, 14, 21, 40 or 60 days of age and brains dissected into 12 regions, including striatum, nucleus accumbens, hypothalamus, thalamus, ventral (tegmentum) and dorsal (tectum) midbrain, hippocampus, frontal, parietal/temporal, and occipital cortices, cerebellum and brain stem for regional Pb analyses. All brain regions generally accumulated Pb in a similar pattern. Regional elimination half-lives, determined for the 350, 1000 and 2000 ppm exposure groups, averaged about 20 days and did not vary between regions. Regional brain Pb levels were not different whether brains were perfused or not prior to brain Pb determinations. However, regional differences in brain Pb levels could be introduced by using dry, rather than wet weights in the calculation of Pb concentrations, and by procedures including soaking in formaldehyde prior to drying, probably as a result of the differential fluid volume of different brain regions. Taken together, these data do not support previous findings of selective regional accumulation of Pb in any brain region, including the hippocampus, at least under conditions of postnatal Pb exposure and wet weight measures. While there may indeed be differences among brain regions in sensitivity to Pb, any differences in response among brain regions should probably be ascribed to differences in the interactions of Pb with biochemical or cellular targets unique or enriched in that region rather than to differences in accumulation of Pb.