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View Full Version : Brain effects of BMP - ALERT! What do you make of this research for "us"?



Back-out
07-12-2010, 03:10 PM
By "us" I mean "spinies" - especially those of us whose fusions include (will include) BMP.

When I first read this article, I thought surely the BMP referred to, must be some hitherto unheard of "BRAIN morphogenetic protein" but, no, it's the same "BONE MP" we've all heard of in spinal fusions. Weird. And even more important for us, than most.

Fascinating research, since it seems everyone's brains are slowed as we age, by BMP. One more process explaining how and why we experience cognitive decline over time. I take from it, one important fact (of particular relevance to us), and many questions.

Fact: Yet one more VERY important reason to exercise after fusion surgery!

Questions:
1) Does the BMP applied (how?) to our bones during surgery, cross the blood/brain barrier?
2) If so, how much more are we exposed to than by the general mechanism (whatever that is)?
3) What is the most helpful - and safe - AEROBIC exercise we can do after surgery (and how can this be increased as we fuse and have fewer limitations)?

I've read elsewhere that some surgeons apply "too much" BMP to the cut bones during surgery (inside the cages?) and that this can hamper the healing process.

I hope surgeons are paying attention to this research! Quite apart from THE great moderating social factor of BMP's prohibitive cost, it seems there is an even more important reason to use as low an effective dose as possible. (I sure can't afford to contend with even more of this natural slowing than already.)

Unfortunately, experience teaches me that policy makers in all areas, are mostly affected by ST (short term) calculations of success in given specialties (what else determines their own rewards?). This focus on ST/limited problem solutions, is IMO one of the main problems in the modern world. It's a demonstrable general "economic" flaw in individual and group decision making.

At least, I'm glad to have learned of this research about BMP. It's not just another "Cassandra finding", but comes with definite practical advice for everyone and (probably) especially for us. After all, chances are, we're much more exposed than average to BMP.

Now, to find out how we can most effectively turn that BMP brain "switch" to the OFF position! It certainly IS a great challenge when the more exposed population, are also more limited by the "nature of the Beast" in maintaining aerobic exercise. (And so far, it DOES appear to be aerobic exercise that does the most to reverse what I now think of as the "Lethargy effect" of BMP!) And yet, chances are, we need more "Noggin"! (Great name)

Encouraging to note that some of the most telling research comes from the Washington U Dept of Neurology. I dare say the spinal folks in the School of Medicine there - think Lenke/Bridwell, et al - will be even more apt to examine these questions about BMP exposure in their patient cohort. Expect they will be adding basic tests of cognitive function to their base-line evaluation and follow-ups. And I hope they will be testing some spinally fused rats who've been treated with BMP! Let's see how well (or poorly) they age compared to controls.

Meanwhile, I'm certainly that much MORE motivated to keep my treadmill free of dust! :eek:

http://well.blogs.nytimes.com/2010/07/07/your-brain-on-exercise/

skevimc
07-12-2010, 04:08 PM
Questions:
1) Does the BMP applied (how?) to our bones during surgery, cross the blood/brain barrier?
2) If so, how much more are we exposed to than by the general mechanism (whatever that is)?
3) What is the most helpful - and safe - AEROBIC exercise we can do after surgery (and how can this be increased as we fuse and have fewer limitations)?

At least, I'm glad to have learned of this research about BMP. It's not just another "Cassandra finding", but comes with definite practical advice for everyone and (probably) especially for us. After all, chances are, we're much more exposed than average to BMP.

Now, to find out how we can most effectively turn that BMP brain "switch" to the OFF position! It certainly IS a great challenge when the more exposed population, are also more limited by the "nature of the Beast" in maintaining aerobic exercise. (And so far, it DOES appear to be aerobic exercise that does the most to reverse what I now think of as the "Lethargy effect" of BMP!) And yet, chances are, we need more "Noggin"! (Great name)

Encouraging to note that some of the most telling research comes from the Washington U Dept of Neurology. I dare say the spinal folks in the School of Medicine there - think Lenke/Bridwell, et al - will be even more apt to examine these questions about BMP exposure in their patient cohort. Expect they will be adding basic tests of cognitive function to their base-line evaluation and follow-ups. And I hope they will be testing some spinally fused rats who've been treated with BMP! Let's see how well (or poorly) they age compared to controls.

Meanwhile, I'm certainly that much MORE motivated to keep my treadmill free of dust! :eek:


Interesting finding. I don't know much about the way BMP is used during surgery however I do study the effects of exercise on muscle and metabolism. So I find this study very interesting. I need to read up on BMP and specifically to see how it normally circulates in the body, e.g. what produces it, how does it circulate, what increases production.

From a totally naive position, I would imagine that some BMP does enter the blood stream as a result of the surgery. I would also assume that it does cross the blood brain barrier since the receptors are on neuronal cells. But does this short term exposure influence anything in the long-term? My hunch would be that if it does affect anything it would be very minimal to the point of being unmeasurable. These types of studies looking at mice and memory are usually more long-term studies (a couple of weeks for mice/rats is a pretty long time). Also, animal studies are given larger doses in order to ensure an effect. the amount of Noggin or BMP given is probably 2 or 3 times the amount that would normally be present.

Anyway, I'm interested to read a bit more about it. I'll post again if I find something.

I'll also reiterate that I know nothing about BMP. I'm just speaking from a general experimental standpoint and what I know about animal experimental design. :)

Back-out
07-12-2010, 06:28 PM
... So I find this study very interesting. I need to read up on BMP and specifically to see how it normally circulates in the body, e.g. what produces it, how does it circulate, what increases production.

From a totally naive position, I would imagine that some BMP does enter the blood stream as a result of the surgery. I would also assume that it does cross the blood brain barrier since the receptors are on neuronal cells. But does this short term exposure influence anything in the long-term? My hunch would be that if it does affect anything it would be very minimal to the point of being unmeasurable. These types of studies looking at mice and memory are usually more long-term studies (a couple of weeks for mice/rats is a pretty long time). Also, animal studies are given larger doses in order to ensure an effect. the amount of Noggin or BMP given is probably 2 or 3 times the amount that would normally be present.

Anyway, I'm interested to read a bit more about it. I'll post again if I find something.

I'm glad you saw this, and very much look forward to your future feedback on these studies! Please note that though this is only one article, in fact, it is an overview of extensive research from numerous individual studies - even groups of studies!

I too am assuming BMP crosses the blood/ brain barrier from surgical exposure. For one thing, except for brain surgery, it could hardly be introduced to the body with more circulatory exposure. It's hardly the casual commercial exposure (of which so much is made, ignorantly) in products humans use topically or through ingestion.

Also, as you pointed out, the target cells under study are neuronal receptors. Hence, this key finding about stem cells governing neurogensis (To me, THE single-most encouraging medical research in a very long time, is that demonstrating the possibility for on-going neurogenesis and neuroplasticity! I speak as an aging American increasingly concerned about dementia and cognitive decline).

You speak of "short term effects", However, it's clear that the BMP introduced in surgery, acts very long term, in this targeted therapeutic use. How else could "packing" the cages with BMP material (however that occurs) exercise the effect of promoting bone fusion on the cut bone ends? This process takes upwards of a year and the effect of that contact exposure during surgery must be considered permanent, at least, en site. It sounds like it genetically modifies the bone cells. Can't get more long term than that!

Of course, maybe that's the result of one-time BMP exposure which is absent soon after permanently changing the bone cells on contact. I know almost nothing about stem cells. That must be a simply WHOPPING one time exposure, though - compared to what is naturally produced.

I'm seriously rethinking whether I welcome that exposure...So little is known about the long-term effects and here definite proof is emerging that BMP exposure is far from benign. Surgeons really jumped on the bandwagon, but how much is really known about how it affects other cells? Here it is, apparently having a very serious negative effect on a far-flung (but rather important) organ - the BRAIN!

Something tells me that if this surgery were more routine, this BMP use would be banned until its effects were more thoroughly understood - as shown in these studies.

The manufacturer and stock-holders would surely raise a great hue and cry first, though. They don't have to hire a single lobbyist, though, because our population is too small and docile. Um, female too, come to think of it - or is that redundant? :p Heh, if BMP were a treatment for prostate problems, I wonder how public reaction would differ.

True, what you wrote about rat experimentation but this doesn't mean the findings don't apply to humans. I doubt there would be such a plethora of studies developing and expanding on these findings about the brain proteins in question, if the basic study premises were that easily dismissed. Indeed, this is the primary mechanism by which all psychotropic medications are tested - except for the more limited (by ethical considerations among much else) studies involving human subjects under controlled conditions.

Perhaps if they find a way of measuring human exposure to BMP, we can get more directly pertinent information. If there isn't a measurable circulating amount of a material to test, it becomes so much harder to check human exposure levels. When we want to understand the effect of a complex protein, acting on the brain, it's almost impossible. We can't "sacrifice" human subjects to examine their brain tissue! As you know, that's the main reason it's so hard to test the influences of various (potential) treatments for Alzheimers. Hard to wait for autopsy results and there's only so much PET scans can reveal.

Hoping you can find time to actually look up some of these studies, and give us the benefit of your trained insights! There seem to be so many of them. Stem cell research is such big business and attracts so many research grants these days. After all, this could potentially lead to major (profitable) breakthroughs in longevity/quality of life research. Imagine it were possible to block the brain effects of BMP without going to the trouble of breaking a sweat! (Of course, that might not be desirable for our population...)

And what if "Noggin" (or an effective precursor) were able to be produced and marketed in a utilizable form! Seems they already planned for that possibility with the naming. :cool:

skevimc
07-12-2010, 07:05 PM
I'm glad you saw this, and very much look forward to your future feedback on these studies! Please note that though this is only one article, in fact, it is an overview of extensive research from numerous individual studies - even groups of studies!


I tracked down the article that the Times author was initially discussing. One published this month in Cell Stem Cell. I hardly ever trust magazine or newspaper authors when they talk about science articles.




You speak of "short term effects", However, it's clear that the BMP introduced in surgery, acts very long term, in this targeted therapeutic use. How else could "packing" the cages with BMP material (however that occurs) exercise the effect of promoting bone fusion on the cut bone ends? This process takes upwards of a year and the effect of that contact exposure during surgery must be considered permanent, at least, en site. It sounds like it genetically modifies the bone cells. Can't get more long term than that!


Yeah... that's a good point. My ignorance is definitely apparent. What I briefly read though is that BMP can be 'contained' in a collagen matrix. So if they are using a 'cage' like you say, this is probably the way the BMP's are placed. Essentially they would be bound in a mesh. Once there, the BMP's would most likely not circulate since they are the cells that stimulate the bone growth, i.e. if they leave, then nothing will tell the bone cells to grow. But here again I could be WAY off.




Of course, maybe that's the result of one-time BMP exposure which is absent soon after permanently changing the bone cells on contact. I know almost nothing about stem cells. That must be a simply WHOPPING one time exposure, though - compared to what is naturally produced.


This is why I can see that the BMP's do not enter the blood stream. Without these to stimulate the osteoblasts (bone stem cells) to form new bone, there's nothing else there. Therefore I'd think the BMP's are meant as a local treatment versus systemic. The question would be how many, if any, BMPs would be able to free themselves from the collagen mesh? And thus make their way up to the brain.



True, what you wrote about rat experimentation but this doesn't mean the findings don't apply to humans. I doubt there would be such a plethora of studies developing and expanding on these findings about the brain proteins in question, if the basic study premises were that easily dismissed. Indeed, this is the primary mechanism by which all psychotropic medications are tested - except for the more limited (by ethical considerations among much else) studies involving human subjects under controlled conditions.


Just to clarify, I wasn't saying the animal studies made the results any weaker. But was in response to the transient versus long-term exposure to various proteins. In animal studies, so that they can be sure to get a response, they expose the animal to a level of protein that is probably way more than anything the body is likely to see in real life. Indeed, the 2010 article exposed the mice for 3 to 4 weeks of Noggin. In a dish and in the mouse itself. This is where it showed that the stem cells eventually wore out. They did this to see if the treadmill induced Noggin increases yielded a similar result.

More as I come across it....

Doodles
07-12-2010, 10:29 PM
Yikes! They put 12 tubes of the stuff in me. It goes along the whole spine. I have 2 cages but it's not just for that I'm pretty sure. I was the one just last week complaining I now have the metabolism of a slug--a dead one--despite all the exercising I do. Janet

Back-out
07-13-2010, 01:07 AM
Yikes! They put 12 tubes of the stuff in me. It goes along the whole spine. I have 2 cages but it's not just for that I'm pretty sure. I was the one just last week complaining I now have the metabolism of a slug--a dead one--despite all the exercising I do. Janet
I remember!

But not to panic. What concerns me about these studies, is the possibility (NOT documented) that the demonstrated causal effect between BMP exposure and cognitive slowing, can be triggered by exposure to it in surgery.

However, it is entirely speculative that even direct BMP application (within the body) will ever reach the brain and stem cells there capable of neurogenisis - only recently recognized as an on-going process. (And one apparently needed to keep our brains "nimble" - to borrow one of the author's clever metaphors)

Much as I argue for the importance of RESEARCHING this possibility (in light of these recent findings), it is uncertain that such large protein molecules can bridge the all-important blood-brain barrier and act directly on the brain.

It 's hard to "apply" materials directly to the brain. In the case of stem cells, we've been unable to get them to target areas there. For example, Parkinson's disease has been shown to respond to stem cells but the only way found to get them inside the brain has been (brain) surgery! Only quite recently, did a breakthrough occur whereby it was found possible to inject such cells through the eyeballs! Likewise, the mice described had "Noggin" injected into their brains.

But most to the point, the effect I 'm worried about is the demonstrated COGNITIVE slowing caused by BMP. BMP has not been shown to cause any generalized METABOLIC slowing like you described. And problematic as that could be for weight control, it's not at all the same. Indeed, I know of nothing that can cause a reduction of the metabolic setpoint, except interference with thyroid production (worth checking, BTW).

Which reminds me, the very fact that you popped out with a neat visual and semantic pun, belies concern about your wit (and cognitive function)! Janet, you're no poster child for the mental dulling hypothesis! :D

titaniumed
07-13-2010, 02:53 AM
Me three! BMP was used extensively, inserted in sponges, inside "Peek" spacers from L1 down to the sacrum.

Funny how my surgeon would finally decide upon my blood work. He told me that since I was athletic all of my life, that my surgeries would work. It showed in my blood analysis.

I have to admit that I battled fatigue for approx 2 years after my surgeries. I was so tired, all the time. I no longer need the afternoon naps everyday. I run around all day long now, and wont sit at my desk all through the day. I changed my work habits, and yes, stuff piles up and I donít care. I will not hesitate to walk to the other end of the building, and encourage a fast walk. I love it when the non-scolis cannot keep up especially the ones half my age.

My surgeon insisted on outdoor exercise and had the PT girl out at my house everyday after my surgeries. Since I elected not to go to a rehab facility, I'm sure he was following her reports every day. I was really whooped after, and she was pushing for action every day. Broken shoulders make walkers difficult so it was decided to scrap the walker and I switched to ski poles.

Janet, keep it going.... things will improve. All we can do is keep pushing on. My second year, or last 10% was the fine tuning of my recovery, the last stretch of the run, which needs to be finished.
Ed

Doodles
07-13-2010, 01:26 PM
It's always encouraging to hear that improvement continues into second year and sometimes beyond! And, that I'm not alone on the fatigue factor. Janet

Susie*Bee
07-13-2010, 01:51 PM
It's always encouraging to hear that improvement continues into second year and sometimes beyond! And, that I'm not alone on the fatigue factor. Janet

Janet-- I've gotten more and more energy and capabilities with each year. No, I'm not lifting 75 pound rocks, but am doing much more than I had been. Looking forward to year 4. :)

Doodles
07-13-2010, 03:28 PM
Thanks Susie Bee. That's good to know. Janet