Accumulation of Manganese in Rat Brain Following Intranasal Administration

Gerald Gianutsos, Gale R. Morrow, John B. Morris
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Abstract

Manganese chloride (50–800 μg) 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 μg 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.

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鼻内给药后大鼠脑内锰的积累
采用大鼠右鼻孔单侧注射氯化锰(50 ~ 800 μg),观察其在中枢神经系统的蓄积量。脑锰水平以剂量依赖、时间依赖和组织依赖的方式升高。在注射后12小时内,在右侧嗅球和嗅结节中检测到锰水平升高,并保持升高至少3天。只需100 μg的氯化锰就足以增加大脑中的锰含量。左脑没有发现任何变化。急性给药后,纹状体(锰神经毒性的靶部位)的锰含量没有变化,但间隔1周两次注射时,锰含量升高。这些结果表明,空气中的锰可以沿嗅觉神经元逆行运输到中枢神经系统,并可以在适当的暴露条件下到达更深的脑结构。
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