Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults.

Confounding neurodegenerative effects of manganese for in vivo MR imaging in rat models of brain insults.

Bouilleret V, Cardamone L, Liu C, Koe AS, Fang K, Williams JP, Myers DE, O'Brien TJ, Jones NC.

J Magn Reson Imaging. 2011 Oct;34(4):774-84

Manganese-enhanced magnetic resonance imaging (MeMRI) is an exciting new technique which is being adopted by many groups.  However, there is not yet a consensus on appropriate dosages, number of repeat administrations, etc.  This is important because high levels of manganese can be neurotoxic, leading to a condition known as manganism.  Somewhat similar to parkinson’s disease, manganaism presents with motor controls, neurodegeneration, and psychiatric disturbances.  To examine the cumulative effects of repeated treatments with a high concentration of manganese, this paper compares the effects of repeated standard MRI (sMRI) with repeated MeMRI.

They used lateral fluid percussion injury (FPI, something akin to a mini squirt gun, at over 3 atmospheres, shot directly in to the sensory-motor cortex) in rats.  These rats were then monitored for anxiety, motor abilities, depression, stress responsivity, epilepsy, weight, etc.  One group was given sMRI scans at one week before, and one week, one month, three months, and six months after the injury.  The other group underwent MEMRI (100mg/kg intraperitoneally, 24hrs pre-scan) at one week before, and one day, one week, one month, and six months after the injury.

MEMRI did not change neuromotor scores during the 3 days following the injury, but it did result in a significantly lower body weight than sMRI controls.  Lower weight gain was also seen in FPI sMRI rats when compared to sham-injury sMRI controls. The same effect was seen with the increases in brain volume at the one month and six month points.  The greatest regional effects corresponded to the areas injured by FPI, suggesting that manganese toxicity may occur in cells which have already sustained insult.

The MEMRI rats showed a strong increase in anxiety over sMRI rats (per elevated plus maze test, time spent in closed arms), as well as significant increase in depression-like behavior (decreased consumption of sucrose water). Interestingly, Mn2+ treatment seemed to lead to a decrease in post-traumatic stress epilepsy.

-DH