Dorman David C, Struve Melanie F, Wong Brian A, Dye Janice A, Robertson Ian D
CIIT Centers for Health Research, 6 Davis Drive, Research Triangle Park, NC 27709-2137, USA.
Toxicol Sci. 2006 Jul;92(1):219-27. doi: 10.1093/toxsci/kfj209. Epub 2006 Apr 25.
High-dose manganese exposure is associated with parkinsonism. Because manganese is paramagnetic, its relative distribution within the brain can be examined using magnetic resonance imaging (MRI). Herein, we present the first comprehensive study to use MRI, pallidal index (PI), and T(1) relaxation rate (R1) in concert with chemical analysis to establish a direct association between MRI changes and pallidal manganese concentration in rhesus monkeys following subchronic inhalation of manganese sulfate (MnSO(4)). Monkeys exposed to MnSO(4) at > or = 0.06 mg Mn/m(3) developed increased manganese concentrations in the globus pallidus, putamen, olfactory epithelium, olfactory bulb, and cerebellum. Manganese concentrations within the olfactory system of the MnSO(4)-exposed monkeys demonstrated a decreasing rostral-caudal concentration gradient, a finding consistent with olfactory transport of inhaled manganese. Marked MRI signal hyperintensities were seen within the olfactory bulb and the globus pallidus; however, comparable changes could not be discerned in the intervening tissue. The R1 and PI were correlated with the pallidal manganese concentration. However, increases in white matter manganese concentrations in MnSO(4)-exposed monkeys confounded the PI measurement and may lead to underestimation of pallidal manganese accumulation. Our results indicate that the R1 can be used to estimate regional brain manganese concentrations and may be a reliable biomarker of occupational manganese exposure. To our knowledge, this study is the first to provide evidence of direct olfactory transport of an inhaled metal in a nonhuman primate. Pallidal delivery of manganese, however, likely arises primarily from systemic delivery and not directly from olfactory transport.
高剂量锰暴露与帕金森症有关。由于锰具有顺磁性，可使用磁共振成像（MRI）检查其在脑内的相对分布情况。在此，我们开展了首个综合性研究，联合使用MRI、苍白球指数（PI）和T(1)弛豫率（R1）以及化学分析，以确定恒河猴在亚慢性吸入硫酸锰（MnSO₄）后MRI变化与苍白球锰浓度之间的直接关联。暴露于≥0.06 mg Mn/m³ MnSO₄的猴子，其苍白球、壳核、嗅上皮、嗅球和小脑中的锰浓度升高。MnSO₄暴露猴子嗅觉系统内的锰浓度呈现出从吻侧到尾侧递减的浓度梯度，这一发现与吸入锰的嗅觉转运一致。在嗅球和苍白球内可见明显的MRI信号高强化；然而，在其间组织中未发现类似变化。R1和PI与苍白球锰浓度相关。然而，MnSO₄暴露猴子白质锰浓度的增加混淆了PI测量结果，可能导致对苍白球锰蓄积的低估。我们的结果表明，R1可用于估计脑内区域锰浓度，可能是职业性锰暴露的可靠生物标志物。据我们所知，本研究首次提供了非人类灵长类动物中吸入金属直接通过嗅觉转运的证据。然而，锰向苍白球的输送可能主要源于全身输送，而非直接来自嗅觉转运。
