Wednesday, 31 July 2013

Too much brain Iron may be bad for the nerves

Hametner S, Wimmer I, Haider L, Pfeifenbring S, Brück W, Lassmann H. Iron and neurodegeneration in the multiple sclerosis brain.Ann Neurol. 2013 Jul 19. doi: 10.1002/ana.23974. [Epub ahead of print]
Objective: Iron (pronounced eye-urn) may contribute to the pathogenesis and progression of multiple sclerosis (MS) due to its accumulation in the human brain with age. Our study focused on non-heme iron distribution and the expression of the iron-related proteins ferritin, hephaestin and ceruloplasmin in relation to oxidative damage in the brain tissue of 33 MS and 30 control cases. 
Methods: We performed (1) whole-genome microarrays including 4 MS and 3 control cases in order to analyze the expression of iron-related genes, (2) non-heme iron histochemistry, (3) immunohistochemistry for proteins of iron metabolism and (4) quantitative analysis by digital densitometry and cell counting in regions representing different stages of lesion maturation. 
Results: We found an age-related increase of iron in the white matter of controls as well as in patients with short disease duration. In chronic MS, however, there was a significant decrease of iron in the normal appearing white matter (NAWM) with disease duration, when corrected for age. This decrease of iron in oligodendrocytes and myelin was associated with an up-regulation of iron-exporting ferroxidases. In active MS lesions, iron was apparently released from dying oligodendrocytes, resulting in extracellular accumulation of iron and uptake into microglia and macrophages. Iron-containing microglia showed signs of cell degeneration. At lesion edges and within centers of lesions, iron accumulated in astrocytes and axons. 
Interpretation: Iron decreases in the NAWM of MS patients with increasing disease duration. Cellular degeneration in MS lesions leads to waves of iron liberation, which may propagate neurodegeneration together with inflammatory oxidative burst. 
 
It is well known that there are changes in iron deposition in the brains of MSers and iron is important to brain health as the blood vessels have transporters to get iron into the brain. This study shows that too much may be bad for glial cells in a complexway which you can read above.

6 comments:

  1. A glass half full study for me MD :-)

    Regards as always

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  2. What conclusions can we draw from you illustrating your interpretation of the study with an image of what appears to be iron pyrite/fools gold?

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    1. You may be over-interpreting there ;-)

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    2. You are giving me too much credit here

      but. Obvioisly touched a sensitive nerve

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  3. Correct me if I misunderstood this post, but it seems that the study's results are further evidence against the venous insufficiency theory of MS.

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    1. You would think so (I've read the full paper) but I'm sure the usual suspect would disagree!

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