Columbia Un-how endothelium regulates cerebral blood flow

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Columbia Un-how endothelium regulates cerebral blood flow

Postby cheerleader » Fri Jun 13, 2014 9:03 am

Really, really interesting, multi-disciplinary study. They damage the endothelium with a laser, creating oxidative stress, and showed how endothelial dysfunction kept the blood vessels from dilating---thus limiting blood flow. Endothelial dysfunction might be the first step in neurological disease. Here's a new group for the ISNVD!

Columbia Engineers Provide New Insight into How the Brain Regulates Its Blood Flow

In a new study published online in the Journal of the American Heart Association June 12, 2014, researchers at Columbia Engineering report that they have identified a new component of the biological mechanism that controls blood flow in the brain. Led by Elizabeth M. C. Hillman, associate professor of biomedical engineering, the team has demonstrated, for the first time, that the vascular endothelium plays a critical role in the regulation of blood flow in response to stimulation in the living brain.

“We think we’ve found a missing link in our understanding of how the brain dynamically tunes its blood flow to stay in sync with the activity of neurons,” says Hillman, who has a joint appointment in Radiology. She is also a member of the Zuckerman Mind Brain Behavior Institute and the Kavli Institute for Brain Science at Columbia. Hillman has spent more than 10 years using advanced imaging tools to study how blood flow is controlled in the brain. “Earlier studies identified small pieces of the puzzle, but we didn’t believe they formed a cohesive ‘big picture’ that unified everybody’s observations. Our new finding seems to really connect the dots.”

“Our finding unifies what is known about blood flow regulation in the rest of the body with how it is regulated in the brain,” Hillman explains. “This has wider reaching implications since there are many disease states known to affect blood flow regulation in the rest of the body that, until now, were not expected to directly affect brain health.”

“Our latest finding gives us a new way of thinking about brain disease—that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels,” Hillman adds. “This gives us a new target to focus on to explore treatments for a wide range of disorders that have, until now, been thought of as impossible to treat. The brain’s vasculature is a critical partner in normal brain function. We hope that we are slowly getting closer to untangling some of the mysteries of the human brain.”


http://engineering.columbia.edu/columbi ... blood-flow


Full paper A Critical Role for the Vascular Endothelium in Functional Neurovascular Coupling in the Brain
http://jaha.ahajournals.org/content/3/3/e000787.full

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Re: Columbia Un-how endothelium regulates cerebral blood flo

Postby ThisIsMA » Fri Jun 13, 2014 1:00 pm

Great find Cheer! It's really encouraging that researchers are beginning to focus on this.

I always thought it was really strange that when my MRI came back showing "slowed brain perfusion", they didn't even discuss it with me, let alone suggest things I could do to try to improve the situation!

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Re: Columbia Un-how endothelium regulates cerebral blood flo

Postby ThisIsMA » Fri Jun 13, 2014 1:21 pm

Hi Cheer,

From the study you linked to above (second link in your post) I read this quote:

The role of the vascular endothelium in blood flow modulation is well characterized in the peripheral vasculature,8,19–22 particularly the ability of the endothelium to propagate vasodilation.

And I'm amazed that "they" by which I mean medical scientists in general, wouldn't ASSUME that the same process was at work in the brain as has already been characterized in the peripheral vasculature endothelium, unless proven otherwise. After all, our bodies are one organism. It makes sense that the endothelium in one part of the body would behave the same as the endothelium as another part of the body.

Instead it sounds like neurologists had been looking far and wide to come up with a nonvascular explanation for what causes blood flow to increase locally in the brain when neuronal activity increases, when it was already known that the endothelium was responsible for causing blood flow to increase in other parts of the body.

This is a classic example of why interdisciplinary education and research collaboration should be the norm, not the exception. I'm glad they're finally figuring it out.

And here's a quote from the first article you linked to above:

Hillman found that the vascular endothelium, the inner layer of blood vessels, plays a critical role in propagating and shaping the blood flow response to local neuronal activity. While the vascular endothelium is known to do this in other areas of the body, until now the brain was thought to use a different, more specialized mechanism and researchers in the field were focused on the cells surrounding the vessels in the brain.

“Once we realized the importance of endothelial signaling in the regulation of blood flow in the brain,” Hillman adds, “we wondered whether overlooking the vascular endothelium might have led researchers to misinterpret their results.”

“As we identified this pathway, so many things fell into place,” she continues, “We really hope that our work will encourage others to take a closer look at the vascular endothelium in the brain. So far, we think that our findings have far-reaching and really exciting implications for neuroscience, neurology, cardiovascular medicine, radiology, and our overall understanding of how the brain works.”

I hope that neurologists have a way to find, read and understand the implications of that article and research study.

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Re: Columbia Un-how endothelium regulates cerebral blood flo

Postby cheerleader » Fri Jun 13, 2014 4:48 pm

Hey M.A.--
That's interesting they noted your slowed perfusion, but didn't say any more about it. I'm sure you know, there's lots you can do to help perfusion--aerobic exercise, eating well, hydration, good sleep, meditation, soaking in a tub....all have science behind them showing the increase in cerebral blood flow. Looks like venoplasty to improve CCSVI can help too, according to Dr. Zamboni's new SPECT/PET pilot study. https://www.youtube.com/watch?v=6dl7ztBgkGw

Neuros have always said that the hypoperfusion we see in MS is simply due to loss of neurons. End of story. MS kills neurons, so people with MS need less blood flow. That's their chicken and egg explanation.

What this study showed is that it is the vascular endothelium that controls the amount of blood going to the brain....blood flow is not initiated by the neurons sending out messages according to their need for glucose or O2...it's initiated by the health of the endothelium.

They proved this by literally frying some endothelial cells with a laser-- imitating what happens during oxidative stress and endothelial dysfunction-- and noting that the blood vessel could then only open up, or dilate, to a fixed level. THIS is what restricted the flow of blood to the brain. It had nothing to do with neuronal needs.

I'm just happy to see researchers looking at the health of the endothelium, and finding correlations between the neurological complications we see in vascular dementia, Alzheimers, diabetes and other neurodegenerative disease. The endothelium connects the whole body---our brains do have a specialized protective system, called the blood brain barrier...but the BBB has endothelial cells, just like every other part of the 60,000 miles of blood vessels in our bodies.
http://ccsvi.org/index.php/helping-myse ... ial-health
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Re: Columbia Un-how endothelium regulates cerebral blood flo

Postby cheerleader » Sat Jun 14, 2014 10:56 am

Dr. Zamboni has the paper now---he is interested to see that perhaps research is moving away from purely neuron-centric approach to neurovascular disease.
https://twitter.com/zambo57

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Re: Columbia Un-how endothelium regulates cerebral blood flo

Postby 1eye » Sun Jun 15, 2014 6:30 pm

I am also concerned about a neuro-centric approach when the blood supply (and drainage) are often ignored.

One area of research that has been revived recently is the venous equivalents of arterial blood flow control mechanisms. This paper goes in the direction of looking at blood flow as a whole, controlled by that ubiquitous organ called the endothelium. This is a good direction for research,

But it concerns me to see the venous side of this story being again given short shrift. The endothelium should be seen as a secondary nervous system and it should be examined from end to end. Oxygen consumption is continuous until the blood has been depleted, and it would be naive to think the endothelium had no role on that end of the system. Oxygen content of blood is likely detected at very low levels, and the level of sensitivity to it must also be continuous, even at very low levels. Certainly the arterial side of this story is important and is a promising are of research. However it would be a mistake to ignore the veins and venules, as much more than oxygen is currency in these systems: there is also sodium, lymph, and spinal fluid, to name a few. To some of these things the venous endothelium is more important. Yet mechanisms and signals may be valid and useful in both sets of vessels.
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Re: Columbia Un-how endothelium regulates cerebral blood flo

Postby Cece » Tue Jun 17, 2014 12:09 am

“Our finding unifies what is known about blood flow regulation in the rest of the body with how it is regulated in the brain,” Hillman explains.

It is frustrating to think that part of why neurological research is so far behind where it should be is because the brain was seen as somehow separate and superior to the rest of the body. What is known about blood flow to other organs is suddenly not known just because it is the brain.
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Re: Columbia Un-how endothelium regulates cerebral blood flo

Postby 1eye » Tue Jun 17, 2014 11:07 am

The lesson for a generalist must be: not to leave stones unturned, just because it is somebody else's job. It's always your job, too. Sorry. Hard to stay ahead of rampant specialism.
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Re: Columbia Un-how endothelium regulates cerebral blood flo

Postby THX1138 » Fri Jun 27, 2014 2:39 pm

They proved this by literally frying some endothelial cells with a laser-- imitating what happens during oxidative stress and endothelial dysfunction-- and noting that the blood vessel could then only open up, or dilate, to a fixed level. THIS is what restricted the flow of blood to the brain. It had nothing to do with neuronal needs.

Sufficient Magnesium is is necessary for muscles to relax properly and fully, smooth muscles of the blood vessels included.
Magnesium is a vasorelaxant.
Few people consume even the minimum recommended amount of magnesium.
I have been told by a doctor that people with ms are magnesium wasters.
The underestimated problem of using serum magnesium measurements to exclude magnesium deficiency in adults; a health warning is needed for "normal" results.
http://www.ncbi.nlm.nih.gov/pubmed/20170394
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