DISTRIBUTION OF BISMUTH IN THE BRAIN AFTER INTRAPERITONEAL DOSING OF BISMUTH SUBNITRATE IN MICE - IMPLICATIONS FOR ROUTES OF ENTRY OF XENOBIOTIC METALS INTO THE BRAIN

Bismuth (Bi) can produce neurotoxic effects in both humans and animals under certain dosing conditions, but little else is known about the e ffects of Bi in the brain. In the present study we determined the dist ribution of Bi in the brains of adult female Swiss-Webster mice 4, 7, 14, 21 and 28 days after a single 2500 mg/kg i.p. injection of Bi subn itrate (BSN), which establishes a depot of absorbable Bi and produces morphological signs of neurotoxicity. Sections of brains were processe d by autometallographic (AMG) procedures that produced silver grains a t the site of Bi localization (AMG(Bi)). Ventricular dilation was obse rved in all BSN-dosed mice. Among treated mice there were marked inter animal differences in the absolute amount of AMG(Bi), but consistent r egional and cellular patterns of AMG(Bi) were observed. AMG(Bi) was ob served in many cell types in brain regions adjacent to fenestrated blo od vessels of the circumventricular organs (CVOs) and olfactory epithe lium. Prominent intrasomal AMG(Bi) was observed in nuclei containing l arge cell bodies, including cranial motor neurons innervating somatic muscle, lateral vestibular and red nucleus and pontine/medullary retic ular nuclei. In the hypothalamus, the supraoptic and paraventricular n uclei demonstrated the densest AMG(Bi). In the cerebellum, Purkinje an d granule cell layers with the densest AMG(Bi) were in folia adjacent to the fourth ventricle. In the hippocampus, AMG(Bi) was densest in th e fasciola cinerum, polymorph cells of the dentate gyrus, and pyramida l cell layer of the CA3 regions. Neuropil of subcortical auditory nucl ei (cochlear nucleus, trapezoid body, lateral lemniscus and nucleus of lateral lemniscus, medial geniculate nucleus and inferior colliculus) had a high density of AMG(Bi). Among nonneuronal cells, ependyma and meninges lining the ventricular and subarachnoid spaces were labeled e xtensively. Glial labeling was prominent adjacent to CVOs, in subepend ymal regions, and in fiber tracts. Presumptive perivascular cells lini ng large blood vessels had extremely dense AMG(Bi) as early as 4 days after dosing. Smaller blood vessels had moderate AMG(Bi). However, in regions (e.g. cerebral cortex, striatum) known to have low brain Bi le vels after i.p. dosing, vascular deposits accounted for most of the AM G(Bi). Several animals had foci of AMG(Bi) which suggested that vascul ar or perivascular aberrations may have contributed to the unusually d ense accumulations. The results of the present studies indicate that B i accumulates predictably in certain regions and cell types. The patte rn of regions and cells with the highest AMG(Bi) accumulations is very similar to pattern reported for other xenobiotic metals (i.e. mercury , silver, gold), and supports the hypothesis that these metals may sha re some mechanisms for entry, distribution and storage in the brain.