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Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Manganese concentration in mouse brain after intravenous injection
1Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Abstract:
Abnormal deposit of manganese (Mn) in the basal ganglia is often observed in patients with chronic liver failure and patients receiving long-term parenteral nutrition. Based on the data that (54)Mn is transported into the brain efficiently via a transferrin-independent uptake system, Mn concentration in mouse brain was determined after intravenous (iv) injection (2 mg Mn/kg/day x 5 times) of either MnCl(2) or pH 8.6 buffer-treated MnCl(2), which has a higher affinity for transferrin than untreated MnCl(2). Brain Mn concentration was significantly increased in either case. Brain Mn concentration of MnCl(2) group was significantly higher than that of pH 8.6 buffer-treated MnCl(2) groups. Mn concentration in the caudate putamen of MnCl(2) group was also significantly higher than that of pH 8.6 buffer-treated MnCl(2) group. Ninety seconds after a single injection of MnCl(2) (2 mg Mn/kg), brain Mn concentration was remarkably increased with blood Mn level, but not 1 hr after injection. On the other hand, hepatic Mn concentration was remarkably high 1 hr after injection and the brain Mn concentration was increased again at 24 hr, followed by decrease of the hepatic Mn concentration. Relative Mn concentrations in the brain 90 sec after injection were different from those 24 hr after injection, suggesting that the mechanism of the increase of brain Mn concentration via blood Mn level is different from that via the redistribution from the liver. Mn ion and/or Mn bound to low molecular weight compounds may be involved in abnormal Mn uptake in the brain.
Insights
Manganese (Mn) accumulation in the brain, particularly the basal ganglia, is linked to liver failure and parenteral nutrition. This study shows Mn uptake in mouse brains occurs via a transferrin-independent pathway, with direct injection leading to higher concentrations than transferrin-bound Mn.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Abnormal manganese (Mn) deposition in the basal ganglia is a hallmark of chronic liver failure and long-term parenteral nutrition.
- Manganese is known to cross the blood-brain barrier via a transferrin-independent uptake system.
Purpose of the Study:
- To investigate the mechanisms of manganese (Mn) brain accumulation.
- To compare Mn brain uptake following direct injection versus transferrin binding.
Main Methods:
- Mice were intravenously injected with either manganese chloride (MnCl2) or pH 8.6 buffer-treated MnCl2 (higher transferrin affinity).
- Brain and blood Mn concentrations were measured at 90 seconds, 1 hour, and 24 hours post-injection.
- Hepatic Mn concentration was also measured to assess redistribution.
Main Results:
- Intravenous MnCl2 injection significantly increased brain Mn concentrations, irrespective of transferrin affinity.
- Directly injected MnCl2 resulted in higher brain Mn levels compared to MnCl2 with higher transferrin affinity.
- Brain Mn levels peaked at 90 seconds post-injection, correlating with blood Mn levels, and showed a secondary increase at 24 hours, suggesting different uptake mechanisms.
Conclusions:
- The brain efficiently accumulates manganese via a transferrin-independent pathway.
- Distinct mechanisms, including direct blood-brain barrier transport and potential hepatic redistribution, contribute to brain manganese accumulation.
- Free manganese ions or those bound to low-molecular-weight compounds may be implicated in abnormal brain Mn uptake.
