Olfactory primary neurons as a route of entry for toxic agents into the CNS
Hastings, L.; Evans, J.E.
Neurotoxicology 12(4): 707-714
1991
ISSN/ISBN: 0161-813X PMID: 1795897 Document Number: 369433
Reports in the literature suggest that the primary sensory neurons of the olfactory system may provide a direct route of entry for agents into the central nervous system (CNS). To investigate whether cadmium, a heavy metal which is normally excluded from the CNS by the blood-brain barrier, can enter the CNS via the olfactory system, rats were exposed either intranasally (unilaterally) or ip to 109Cd (1 .mu.mol Cd labeled with 1 .mu.Ci 109Cd). Rats were allowed to survive 7 days, at which point they were euthanized and the kidneys, livers, right and left forebrains, right and left olfactory bulbs, and right and left olfactory epithelia were removed. Tissues were placed in scintillation vials and radioactivity counted. In rats exposed by intranasal instillation, Cd levels were significantly elevated in the kidney, liver and ipsilateral olfactory bulb and epithelium, but not in the contralateral bulb and epithelium or forebrain areas. With the ip exposure, Cd levels were only elevated in the kidney and liver. In a second study the protocol was repeated (without ip exposure), but the olfactory bulbs and epithelium were washed in EDTA before counting. Cd was still present in the bulbs after washing, suggesting that the metal was internal and not bound to the external membrane. In the final experiment, both time course and dose effect of this phenomenon were explored. Rats were exposed either intranasally to 1 .mu.mol Cd (1 .mu.Ci) and then sacrificed after 1, 3, 7, or 14 days or were exposed to 0.01, 0.1, or 1.0 .mu.mol Cd labeled with 1 .mu.Ci 109Cd and sacrificed after 7 days. Cadmium concentrations in the olfactory epithelium declined steadily after the initial exposure, while in the bulb, concentration peaked at day 7 and then declined. A clear dose effect was observed with increasing exposure. These results indicate that Cd after intranasal intubation can enter the CNS - at least to the olfactory bulbs - via this route.