Accumulation of manganese in rat brain following intranasal administration.
Manganese chloride (50-800 micrograms) was injected unilaterally into the right nostril of rats and its accumulation in the central nervous system (CNS) was monitored. Brain manganese levels were elevated in a dose-dependent, time-dependent, and tissue-dependent manner. Elevated levels of manganese were detected in the right olfactory bulb and olfactory tubercle within 12 hr after instillation and remained elevated for at least 3 days. As little as 100 micrograms of manganese chloride was sufficient to increase brain manganese levels. No changes were detected on the left side of the brain. The manganese content of the striatum, the target site for manganese neurotoxicity, was unchanged following acute administration, but was elevated when two injections were made 1 week apart. These results suggest that air-borne manganese can be retrogradely transported along olfactory neurons to the CNS and can reach deeper brain structures under appropriate exposure conditions.
Gianutsos
G
G
Department of Pharmaceutical Sciences, University of Connecticut School of Pharmacy, Storrs 06269-2092, USA.
Morrow
G R
GR
Morris
J B
JB
D000281:Administration, Intranasal; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000008:administration & dosage / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism*; D017072:Neostriatum / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D009833:Olfactory Pathways / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002712:Chlorides; D017895:Manganese Compounds; C025340:manganese chloride