Bock Nicholas A, Paiva Fernando F, Nascimento George C, Newman John D, Silva Afonso C
Cerebral Microcirculation Unit, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1065, USA.
Brain Res. 2008 Mar 10;1198:160-70. doi: 10.1016/j.brainres.2007.12.065. Epub 2008 Jan 4.
Manganese overexposure in non-human primates and humans causes a neurodegenerative disorder called manganism thought to be related to an accumulation of the metal in the basal ganglia. Here, we assess changes in the concentration of manganese in regions of the brain of a non-human primate (the common marmoset, Callithrix jacchus) following four systemic injections of 30 mg/kg MnCl2 H2O in the tail vein using T1-weighted magnetic resonance imaging (MRI) and compare these to changes in the rat following the same exposure route and dose. The doses were spaced 48 h apart and we imaged the animals 48 h after the final dose. We find that marmosets have significantly larger T1-weighted image enhancements in regions of the brain compared to rats, notably in the basal ganglia and the visual cortex. To confirm this difference across species reflects actual differences in manganese concentrations and not variations in the MRI properties of manganese, we measured the longitudinal relaxivity of manganese (chi1) in the in vivo brain and found no significant species' difference. The high manganese uptake in the marmoset basal ganglia and visual cortex can be explained by CSF-brain transport from the large lateral ventricles and we confirm this route of uptake with time-course MRI during a tail-vein infusion of manganese. There is also high uptake in the substructures of the hippocampus that are adjacent to the ventricles. The large manganese accumulation in these structures on overexposure may be common to all primates, including humans.
非人类灵长类动物和人类体内的锰过量暴露会引发一种名为锰中毒的神经退行性疾病，这种疾病被认为与金属在基底神经节中的积累有关。在此，我们使用T1加权磁共振成像（MRI）评估了普通狨猴（Callithrix jacchus）尾静脉注射4次30 mg/kg MnCl₂·H₂O后大脑区域锰浓度的变化，并将这些变化与相同暴露途径和剂量下大鼠的变化进行比较。剂量间隔为48小时，我们在最后一剂后48小时对动物进行成像。我们发现，与大鼠相比，狨猴大脑区域的T1加权图像增强更为显著，尤其是在基底神经节和视觉皮层。为了确认这种跨物种差异反映的是锰浓度的实际差异而非锰的MRI特性变化，我们测量了活体大脑中锰的纵向弛豫率（chi1），发现物种间无显著差异。狨猴基底神经节和视觉皮层中锰的高摄取可通过来自大侧脑室的脑脊液-脑转运来解释，并且我们在尾静脉输注锰期间通过时间进程MRI证实了这种摄取途径。海马体与脑室相邻的亚结构中也有高摄取。过度暴露时这些结构中大量的锰积累可能在所有灵长类动物（包括人类）中都很常见。
