Inner Healing - Spitting Out Clots to Survive

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Scientists have discovered a unique way in which small blood vessels deal with a blockage: they spit it out.

Clot-busting enzymes often dissolve blood clots and cholesterol that block blood vessels. Researchers have known this for a long time. But no one knew if a protective process may occur in the tiny capillaries of the circulatory system.

One does, and the finding may hold promise in new treatments for stroke and Alzheimer’s patients.  

Dr. Jaime Grutzendler, assistant professor of neurology and physiology at Northwestern University’s Feinberg School of Medicine, discovered the surprising answer about capillaries with his team. They spent more than three years studying how brain tissue reacts to these tiny blockages. Survival, in this case, comes in the form of spitting. Dr. Jaime Grutzendler (above) and other researchers at Northwestern University discovered how capillaries in mice "spit" out blockages, a process that could hold promise for treating stroke and Alzheimer's patients.Dr. Jaime Grutzendler (above) and other researchers at Northwestern University discovered how capillaries in mice "spit" out blockages, a process that could hold promise for treating stroke and Alzheimer's patients.

How did you make this discovery?
Researchers have wanted to know what is going on in smaller blood vessels for a while now. We do know there is this system that employs enzymes to break down clots that block bigger blood vessels, but we wanted to understand what happens in the smaller vessels, the capillaries. Is it this enzymatic method or does the body have another way? We also wanted to know what the consequences were if these vessels were not cleared fast enough or at all. We assumed it caused tissue death, but we weren’t sure.

How did you go about answering these questions?
We essentially created our own tiny clots and made them fluorescent. These clots were then injected into the brains of live mice, where they’d get lodged in these smaller blood vessels. Using various microscope techniques, we’d watch what happens.

Were you expecting to see capillaries behave the way they did?
Obviously not. We had been so focused on the consequences of blockages on surrounding tissue, there was a bit of serendipity when we witnessed this ”new” biological process.

Tell us what you saw.
On the first day, the blockage was visibly lodged in the clot and blood flow was kinked. But on the third day, we noticed that a membrane had formed around the blockage. This membrane originated from the walls of the blood vessel itself. By the fifth day, the capillary had split open and spit out the blockage. So now blood flow was restored. What’s more, the capillary was using part of the leftover membrane as a band-aid to heal its own break.

Microscopic time-lapse photography of a capillary (green) “spitting” a clot (red) over the course of five days. Microscopic time-lapse photography of a capillary (green) “spitting” a clot (red) over the course of five days. Rather than use this “spitting” process, why don’t capillaries use the same enzymatic process we see in larger blood vessels?
We found that these enzymes are only able to break down about 50 percent of the blockages in capillaries. It just does not happen with the same speed or efficiency. We’re not sure why. It could be that they can’t get access to the blockage.

The other issue is the clot itself. They can consist of many different things—fibrin, cholesterol, platelets—and some are harder to dissolve than others. So it depends on what is stuck there in the first place. The known enzymes are only able to break down blood clots made of the protein called fibrin. But there is no known enzyme that can break down blockages of other materials such as cholesterol or calcium plaques. So the mechanism that we discovered is very neat because it can expel all kinds of materials, even tiny plastic microspheres.

After the clot is expelled, did it pose any further danger?
We didn’t answer that particular question, but the danger of blocking the flow of blood to a region of the brain is a larger concern than just having a small piece of junk sitting somewhere in the brain. And actually, what we have seen is that the material does degrade over time, so there are mechanisms in the brain that get rid of the junk. But it’s not an urgent situation anymore.

Your research also found that capillaries in older mice had a harder time clearing blockages. Why?
It didn’t completely surprise me—lots of things go wrong as we age. This process was no different. Right now, we can only speculate as to why capillaries didn’t remove blockages as effectively in older mice. One possibility is that with age, abnormal proteins accumulate around small blood vessels, creating a thicker barrier for the clot to be expelled.

This also brings an interesting possibility. In Alzheimer’s disease, blood vessels accumulate a protein fragment called amyloid, which in theory also could affect the ability to expel clots. If this is shown to be the case - and we are currently investigating this - it would provide a potential explanation for why patients with Alzheimer’s who also have vascular risk factors have a more rapid decline in mental function. The failure of the ejection method in Alzheimer’s patients could add up and make this a vascular form of dementia. 

What’s next?
Well, first, does this even happen in humans? [Laughing.] We’ve only witnessed it in mice. Biologically, there’s not much difference between our blood vessels and those of mice, so I’d be surprised if it didn’t happen in humans. But you still have to prove it.

Finally, is it a truly necessary process to the body? If it is, and you could accelerate the process somehow, I could envision it being very helpful in treating strokes and also in cases of vascular dementia. It may also have relevance in blockages of capillaries in other organs.

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