3 new studies: MS BBB break prior to immune cells

[cheerleader]

1. In vitro study of the direct effect of extracellular hemoglobin on myelin components.
http://www.ncbi.nlm.nih.gov/pubmed/25463632

The cellular biologists from the University of Guelph are looking at how blood particles damage myelin. They are seeing microscopic deposits of hemoglobin in the MS brain, around the veins. This blood contains iron, which when deposited into delicate brain tissue, begins a process of oxidative stress.

"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."

This work confirms the hypothesis of Dr. Zamboni from 2006, called his "Big Idea" theory, which saw the similarities of venous disease to MS, by noting how blood particles caused damage to tissue via the iron found in our red blood cells. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633548/

It also confirms the research of Dr. Yulin Ge of NYU who has noted with 7T MRI microscopic bleeding in the MS brain, preceeding demyelinating lesions.


2. Focal disturbances in the blood brain barrier are associated with formation of neuroinflammatory lesions
http://www.ncbi.nlm.nih.gov/pubmed/25448765

Neurobiologists from the University of Montreal are seeing changes to the blood brain barrier which happen before immune cells enter the MS brain. There are changes to the tight junctions of endothelial cells.

" Our findings suggest that BBB breach occurs before significant immune cell infiltration and demyelination."

3. The Role of Angiogenesis in the Pathology of MS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253611/

Cell biologists from the University of Irvine have noted how the loss of endothelial tight junctions in the blood brain barrier contributes to inflammation and angiogenesis (the growth of new blood vessels) in the MS brain, and how this process is initiated by hypoxia. This low oxygen state and resultant angiogenesis occurs prior to formation of demyelinating lesions.

These studies indicate that angiogenesis takes place early during MS progression, even before formation of lesions with impaired endothelial barrier function.

While astronaut Samantha Cristoforetti uses Dr. Paolo Zamboni's technologies on the International Space Station, in hopes of undestanding venous hypertension in microgravity, and why 20% of astronauts return with neurological and visual disturbances, research into the vascular connection to MS continues on earth in cellular biology labs.
http://ccsviinms.blogspot.com/2014/12/f ... cular.html

cheer

[orion98665]

Excellant find Cheer, Just more compiling evidence ...!!!


Thanks,

Bob

[Scott1]

How do you get the walls of dilated veins into a dish without capillary and venous hemorrhages distorting the result? Wouldn't in vivo studies be better (but harder to do)?

Regards

[cheerleader]

How do you get the walls of dilated veins into a dish without capillary and venous hemorrhages distorting the result? Wouldn't in vivo studies be better (but harder to do)?

Regards

Scott-
The in vivo work for human studies is mostly accomplished by MRI--the high powered 7 Tesla MRI views microhemorrages which dot the MS brain and BOLD and SWIM technologies show hypoxic insult from hypoperfusion. Both are visible on scans before demyelinating lesions appear.

Dr. Yulin Ge began 7T imaging studies for MS in 2008 and saw microvacular involvement--and he presented on even more in press research at ISNVD in February

These findings, which have never been shown on conventional field of MRI, not only allow for direct evidence of vascular pathogenesis in MS in vivo, but have important implications for monitoring lesion activity and therapeutic response.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579786/

The cellular studies, or in vitro research I've linked above, explains the consequences of hypoperfusion, extravasation of blood into the brain, and the break in the blood brain barrier due to endothelial permeability. We have models of these changes in mice, as well as human tissue. New technologies are allowing researchers to follow the succession of events inside people. And MS inflammation begins before immune cell infiltration.
cheer

[Leonard]

cheer, thanks. I think our threads are converging. Leo
http://www.thisisms.com/forum/post231370.html#p231370