Direct olfactory transport of inhaled manganese (54MnCl2) to the rat brain:: Toxicokinetic investigations in a unilateral nasal occlusion model
Direct olfactory transport of inhaled manganese (54MnCl2) to the rat brain:: Toxicokinetic investigations in a unilateral nasal occlusion model
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DOI：
10.1006/taap.2000.9073
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发表时间：
2000-12-15
影响因子：
3.8
通讯作者：
Dorman, DC
中科院分区：
文献类型：
--
作者：
Brenneman, KA;Wong, BA;Dorman, DC
人体吸入高浓度锰（Mn）与基底神经节锰水平升高和锥体外运动障碍有关。在大鼠中，经鼻内注入(MnCl2)-Mn-54后，Mn可通过嗅觉直接从鼻子运输到大脑。然而，这一途径对吸入后脑锰输送的贡献尚不清楚，这也是我们研究的主题。雄性8周龄CD大鼠单次暴露于(MnCl2)-Mn-54气溶胶(0.54 mg Mn/m(3)；MMAD 2.51妈妈)。在暴露后0、1、2、4和8天对鼻子和大脑的左右两侧，包括嗅觉通路和纹状体进行采样。对照大鼠双鼻孔暴露于(MnCl2)-Mn-54以评价Mn传递的对称性。另一组大鼠右鼻孔被堵塞，以防止(MnCl2)-Mn-54在阻塞侧的鼻沉积。采用伽马能谱法（n = 6只大鼠/组/时间点）和放射自显影法（n = 1只大鼠/组/时间点）比较鼻和脑左右两侧的Mn-54水平，以确定嗅觉摄取对脑Mn-54水平的贡献。来自封闭鼻孔一侧的大脑和鼻子样本的Mn-54活性水平可以忽略不计，验证了鼻腔阻塞手术。在吸入暴露后1-2天内，在开放鼻孔一侧或两侧的嗅球和束/结节中观察到高水平的Mn-54。这些结果首次表明，在单次吸入暴露后8天内，大鼠大脑的嗅觉途径中发现的Mn-54的大部分（高达90%）来自嗅觉途径，而纹状体中没有。这些发现表明，嗅觉途径可能对大鼠吸入暴露后的脑锰水平有重要贡献。(C) 2000年学术出版社。
Inhalation exposure of humans to high concentrations of manganese (Mn) is associated with elevated Mn levels in the basal ganglia and an extrapyramidal movement disorder. In the rat, direct olfactory transport of Mn from the nose to the brain has been demonstrated following intranasal instillation of (MnCl2)-Mn-54. However, the contribution this route makes to brain Mn delivery following inhalation is unknown and was the subject of our study. Male 8-week old CD rats underwent a single 90-min nose-only exposure to a (MnCl2)-Mn-54 aerosol (0.54 mg Mn/m(3); MMAD 2.51 mum). The left and right sides of the nose and brain, including the olfactory pathway and striatum, were sampled at 0, 1, 2, 4, and 8 days postexposure. Control rats were exposed to (MnCl2)-Mn-54 with both nostrils patent to evaluate the symmetry of Mn delivery. Another group of rats had the right nostril plugged to prevent nasal deposition of (MnCl2)-Mn-54 on the occluded side. Gamma spectrometry (n = 6 rats/group/time point) and autoradiography (n 1 rat/group/time point) were used to compare the levels of Mn-54 found on the left and right sides of the nose and brain to determine the contribution of olfactory uptake to brain Mn-54 levels. Brain and nose samples from the side with the occluded nostril had negligible levels of Mn-54 activity, validating the nasal occlusion procedure. High levels of Mn-54 were observed in the olfactory bulb and tract/tubercle on the side or sides with an open nostril within 1-2 days following inhalation exposure. These results demonstrated, for the first time, that the olfactory route contributes the majority (up to > 90%) of the Mn-54 found in the olfactory pathway, but not in the striatum, of the rat brain up to 8 days following a single inhalation exposure. These findings suggest that the olfactory route may make a significant contribution to brain Mn levels following inhalation exposure in the rat. (C) 2000 Academic Press.