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study of the effect of hemoglobin on myelin

PostPosted: Wed Dec 03, 2014 10:38 am
by frodo
Just for those of you that love literature, here comes the next chapter of "Hemosiderin damage"

In vitro study of the direct effect of extracellular hemoglobin on myelin components.


There is a relationship between cerebral vasculature and multiple sclerosis (MS) lesions: abnormal accumulations of iron have been found in the walls of dilated veins in MS plaques. The sources of this iron can be varied, but capillary and venous hemorrhages leading to blood extravasation have been recorded, and could result in the release of hemoglobin extracellularly. Extracellular hemoglobin oxidizes quickly and is known to become a reactive molecule that triggers low-density lipoprotein oxidation and plays a pivotal role in atherogenesis. In MS, it could lead to local oxidative stress, inflammation, and tissue damage. Here, we investigated whether extracellular hemoglobin and its breakdown products can cause direct oxidative damage to myelin components in a peroxidative environment such as occurs in inflamed tissue. Oxidation of lipids was assessed by the formation of fluorescent peroxidized lipid-protein covalent adducts, by the increase in conjugated diene and malondialdehyde. Oxidation of proteins was analyzed by the change in protein mass. The results suggest that the globin radical could be a trigger of myelin basic protein oxidative cross-linking, and that heme transferred to the lipids is involved in lipid peroxidation. This study provides new insight into the mechanism by which hemoglobin exerts its pathological oxidative activity towards myelin components. This work supports further research into the vascular pathology in MS, to gain insight into the origin and role of iron deposits in disease pathogenesis, or in stimulation of different comorbidities such as cardiovascular disease.

Re: study of the effect of hemoglobin on myelin

PostPosted: Wed Dec 03, 2014 11:00 am
by cheerleader
Thanks, Frodo--

Great paper.
This fits in with what Dr. Yulin Ge is seeing---tiny micro hemorrages only visible on 7Tesla MRI. Little spots of blood in the MS brain, which precede demyelinating lesions. Which goes back 150 years to what Rindfleisch saw in his microscope. Extravasation of blood. Can we just all please take the vascular connection to MS seriously??

Here's a good thread on microbleeds in the MS brain, with an earlier paper by these same researchers in Canada--

Re: study of the effect of hemoglobin on myelin

PostPosted: Thu Dec 04, 2014 1:16 pm
by 1eye
Whether it's a broken blood-brain-barrier, or a broken blood-vessel is just a matter of degree. In one case you have whole blood and large cells getting through, in the other you may have less iron, smaller cells and molecules. They are both pathological, and may be the source of misplaced immune cells, and iNOS, and NO, outside vessel walls, in brains. I think in "MS" there is also inflammation and more than normal immune activity within blood vessels. Because there are both problems, there are a variety of symptoms. I am very tired of hearing "MS" simplified down to a mere myelin breakdown.