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Vasculogenesis and Angiogenesis

Vasculogenesis of the cerebral vasculature occurs outside the brain with the formation of a perineural plexus, from which capillary sprouts penetrate the neural tube. The subsequent elaboration of the cerebral vasculature occurs by angiogenesis. Cerebral angiogenesis is tightly linked to the proliferation and growth of neurons and glia, and appears to be mediated at least in part by hypoxia-inducible transcription factors (HIFs). HIFs up-regulate the production of vascular endothelial growth factor (VEGF), which in turn stimulates endothelial cell proliferation, migration, and survival. Angiogenesis is down-regulated once the vascular bed is established (shortly after birth), but proceeds at a slower pace throughout life. In animal models, for example, angiogenesis has been observed in the healthy adult brain in response to a variety of stimuli that increase neural activity, including exercise, exposure to enriched sensory environments, and certain hormones. Brain angiogenesis can also undergo dramatic local up-regulation in response to disease states such as brain tumor, stroke, or trauma.

VMBs are characterized by activated angiogenesis.
http://www.ninds.nih.gov/news_and_event ... rkshop.htm

Perivascular microenvironment

Angiogenesis is actively regulated by surrounding tissue cells, and also by resident and circulating immune cells. Angiogenic processes in the CNS are likely to differ from those in other organs, not only because of the specialized parenchymal cell types involved, but also because brain vascular endothelial cells themselves have unique properties. Most prominent of these are (1) the presence of tight junctions and (2) the formation of specialized contacts with astrocyte endfeet. These morphological features contribute to the special permeability properties of blood-brain barrier (BBB), and appear to be disrupted in CCMs.

Formation and maintenance of the BBB requires cross-talk between the cells of the neurovascular unit (i.e., vascular endothelial cells, neurons, astrocytes, and pericytes), much of which appears to be mediated by cell adhesion molecules and molecules of the extracellular matrix. Reciprocal communication between the cells of the neurovascular unit regulates not only BBB formation, but also angiogenesis and neurogenesis. In stroke, for example, there is recruitment of new endothelial cells to ischemic tissue, and new vessels in turn attract neural precursors. Hence, it is possible that defects in signaling between the cells of the neurovascular unit contribute to the development of VMBs, and also to their adverse impact on surrounding neural tissue.

A fourth population of cells likely to be important in VMB pathogenesis is immune cells. VMB lesions frequently show marked infiltrations of inflammatory cells and local up-regulation of inflammatory cytokines, some of which are powerful regulators of angiogenesis and vascular permeability. In addition, polymorphisms in cytokine genes have been associated with increased risk of hemorrhage for sporadic brain AVMs.

Sorry if this is an info-dump!! I am trying to figure some of this out. LDN promotes angiogenesis, which is probably why it's worked for so many...but what the heck is angiogenesis? More than just the promotion of growth of blood vessels (and collaterals?), but the strengthening of the endothelials cells at the blood brain barrier itself? Hypoxia-inducible transcription factors signal for angiogenesis to happen & our brains are in more or less constant states of hypoxia...so there should be lots of angiogenesis going on. And what is this about immune cells/inflammatory cytokines having a role in angiogenesis? For the good or for the bad? Also again here are those adhesion molecules that are essential for the formation and maintenance of the BBB...but how? I do see exercise mentioned and am thinking I should do more of that...that much I understand!

Very interesting indeed. Just saw this TED-talk by Dr. Li on angiogenesis:

His speech focusses mostly on cancer, but actually he lists ms as one of the diseases with excessive angiogenesis. He also has a website: http://www.angio.org/. And his ideas for preventing excessive angiogenesis sound very yummy

thanks for the links, Boreas...I am not sure that we'd want to prevent excessive angiogenesis? I think angiogenesis has been one of the good players in this story...no one is suggesting we ablate the collaterals when we get our jugulars treated, because if the jugulars restenose, the collaterals are the system that will take up the load until we get back to the doctor.

edited to add: wow, great website. Here's a quote from there:
"Therapeutic angiogenesis, in contrast, stimulates angiogenesis where it is required but lacking. This technique is used to replenish the blood supply to chronic wounds to speed healing, and it prevents unnecessary amputations. New research suggests this approach can be also used to save limbs afflicted with poor circulation, and even oxygen-starved hearts. Therapeutic angiogenesis may even help to regenerate damaged or lost tissues in ways that were previously considered impossible, such as with nerves and brain tissue."

This is very interesting, and I am a bit confused. Am a little tired, so maybe not understanding this.

Do we want to increase angiogenisis to help grow new blood vessels to help provide oxygen to our brains?
If so then LDN is a good idea, and we should avoid all of those foods recommended in the presentation from the above link.
(then we need to consider...but does LDN increase the incidence of cancer, by also feeding those little innocuous cancers that we all apparently develop which are not dangerous until they develop vascularization).

Or do we want to inhibit angiogenisis? (and eat all of the foods recommended in the presentation). I thought I noticed that in the presentation from the above link, the suggestion was that we want to reduce angiogenisis in MS.

Brightspot, I am not sure. The way I understand it, our bodies are naturally reacting to the CCSVI condition with angiogenesis; this is how we're able to grow all the spaghetti-cool collaterals. Without the collaterals, we'd be in trouble; no one is suggesting that we ablate the collaterals when we get jugular venoplasty, because if it restenoses those collaterals are our lifeboat. But the collaterals are also implicated as a weak spot where diapedesis (hee) or leakage of blood cells into the brain might be taking place. That MS patients have "excessive" angiogenesis going on compared to normal people is not a surprise, in light of CCSVI.

So I think angiogenesis is good and has played a role in why MSers' health over the years. But, if venoplasty is able to be performed, then that should solve the problem that our bodies are trying to solve via angiogenesis.

I found it interesting too that angiogenesis plays a negative role in eye health, according to info following that link. So it may be that what's benefitting the brain (improvements in collateral drainage) is at the same time damaging the eyes (would have to reread to see how this works).

New Insight Into How The Brain Regenerates After Stroke
ScienceDaily (Dec. 23, 2006) — When a stroke strikes, the supply of blood to the part of the brain affected is interrupted, starving it of oxygen. Brain cells can be seriously damaged or die, impairing local brain function.

But the brain is a battler. Within weeks of a stroke, new blood vessels begin to form, and, like marching ants, newly born neurons migrate long distances to the damaged area to aid the regeneration process. What's not known is what the right cellular environment is, and what the cellular cues are for this process of regeneration and migration to take place.

Now, in the Journal of Neuroscience, currently online, S. Thomas Carmichael, M.D., Ph.D., an assistant professor in the Department of Neurology at the UCLA Geffen School of Medicine, and colleagues report that in the mouse model, this neuron march is the direct result of signaling from the newly blooming blood vessels, thus casually linking angiogenesis the development of new blood vessels and neurogenesis, the birth of new neurons. Further, they have identified what these molecular signals are. The results hold promise for eventual clinical applications that may spur brain repair after stroke."

http://www.sciencedaily.com/releases/20 ... 092924.htm

this neuron march is the direct result of signaling from the newly blooming blood vessels, thus casually linking angiogenesis the development of new blood vessels and neurogenesis, the birth of new neurons.

If there is such a signal, which means 'new vasculature exists, start growing, neurons' there could be a similar signal in place which says 'end of new vein growth, not successful' and makes arterial growth go into limbo.

Quick result [from Liberation]: we need more oxygen. Normal response: build more arteries. Need to build more drainage first to accomodate more used up blood. Build new drain path. Doesn't work because of problem with existing drains (downstream). So go into a wait loop for situation to improve. Veins unblocked [Liberation]. New flow rate is happpening. Come out of wait loop and start building new arteries. Takes a few weeks. Food consumption extremely important for the next while. Meantime more oxygen is present, some symptoms disappear immediately, others must wait, for new arteries and other brain growth/nerve restoration.

Slow result: remission. we need more oxygen. recent or pending corrolary growth in the area means we can get it now, start growing new vessels. Takes a while for both. Remission will never come, if either arteries or veins can't grow. What are the chances we grow a new jugular, hook it up right, and by the way have new valves too? Then grow new arteries? Of course I am leaving out a lot of detail here.