Brain cells in areas targeted by multiple sclerosis may regenerate - often years after the initial injury, according to research by a team of Cleveland Clinic neuroscientists.
The finding, published online today, lends further support for the concept of adult neurogenesis -- that the human brain can regenerate itself, and in the case of MS, is working to repair itself.
Multiple sclerosis is a chronic disease in which the immune system begins to attack the fatty protective barrier around nerve fibers in the central nervous system. When that area, known as the myelin, is destroyed, the impulses traveling along those pathways from the brain or spinal cord can be slowed, distorted, or cut off completely if the nerve itself is injured.
The researchers examined the brains of nine multiple sclerosis patients who donated their organs after death in the hopes of furthering research on the disease,
"The brain is continuously trying to replace what has been destroyed -- not just myelin, but also neurons," said Bruce Trapp, one of the lead authors on the paper and chair of neurosciences at the Lerner Research Institute.
Trapp think the biggest impact of the paper will be just that -- that there is evidence of the neurogenesis in this area of the brain. Many scientists have resisted the increasing amount of evidence that shows regeneration of neurons in other areas of the brain, like the hippocampus, because of a long-held belief that the brain cannot regenerate. In short, you're stuck with what you've got.
"It's a controversial area, and it's something that's very difficult to prove," said Trapp.
Trapp and his team went looking for old MS lesions in the brains they examined, and wanted to know what happened to the neurons in those areas. They weren't surprised that many of them were destroyed, probably as "bystanders" when the myelin was attacked.
"But then we were shocked when we saw areas of old lesions, and these lesions can be decades old, that had very high concentrations of neurons," Trapp said. In one quarter of the lesions they looked at, there was a 72 percent increase in density of interneurons, which are the neurons that communicate locally.
The question of whether a motor neuron, which communicates over a long distance, could regenerate is still an unanswered question.
Trapp's team was able to count the neurons because the white matter is relatively neuron-poor compared to the rest of the brain. They were also able to show that the neurons had made connections to each other through synapses.
But, Trapp doesn't know if the neurons he saw were capable of communicating with one another or were functional.
Source: Cleveland.com ©2008 cleveland.com
I used to hope that I would get better, but that has not happened and I have only gotten worse throughout the years.
If something is really regenerating inside our brains, it is either really slow or is chasing the wrong neurons to be of much help.
gwa:Contact: Jennifer Fitzenberger
University of California - Irvine
Adult stem cells activated in mammalian brain
Locating cell origin provides foundation for brain injury cure
Irvine, Calif., July 24, 2008 — Adult stem cells originate in a different part of the brain than is commonly believed, and with proper stimulation they can produce new brain cells to replace those lost to disease or injury, a study by UC Irvine scientists has shown.
Evidence strongly shows that the true stem cells in the mammalian brain are the ependymal cells that line the ventricles in the brain and spinal cord, rather than cells in the subventricular zone as biologists previously believed. Brain ventricles are hollow chambers filled with fluid that supports brain tissue, and a layer of ependymal cells lines these ventricles.
Knowing the cell source is crucial when developing stem cell-based therapies. Additionally, knowing that these normally dormant cells can be coaxed into dividing lays the groundwork for future therapies in which a patient's own stem cells produce new brain cells to treat neurological disorders and injuries such as Parkinson's disease, stroke or traumatic brain injury.
"With such a therapy, we would know which cells in the body to target for activation, and their offspring would have all the properties necessary to replace damaged or missing cells," said Darius Gleason, lead author of the study and a graduate student in the Department of Developmental and Cell Biology. "It is a very promising approach to stem cell therapy."
Study results appear this month online in the journal Neuroscience.
Stem cells are the "master cells" that produce each of the specialized cells within the human body. If researchers could control the production and differentiation of stem cells, they may be able to use them to replace damaged tissues.
One focus of stem cell research is transplantation, which entails injecting into the body healthy cells that may or may not genetically match the patient. Transplantation of nonmatching stem cells requires the use of drugs to prevent the body from rejecting the treatment.
But, working with a patient's own cells would eliminate the need for transplantation and immunosuppressant drugs and may be a better alternative, scientists say. Ependymal cells line the fluid-filled ventricles, so a drug to activate the cells could theoretically travel through this fluid directly to the stem cells.
"The cells already match your brain completely since they have the same genetic make-up. That is a huge advantage over any other approach that uses cells from a donor," Gleason said. "If they are your cells, then all we are doing is helping your body fix itself. We're not reinventing the repair process."
In this study, Gleason and Peter Bryant, developmental and cell biology professor, used rats treated to develop the animal equivalent of Parkinson's disease. They chose this type of rat because in a previous study by UCI collaborator James Fallon, a small protein given to the brain-damaged rats sparked a rapid and massive production and migration of new cells, and significantly improved motor behavior.
First, the UCI researchers sought to determine the true location of stem cells in the rats by looking for polarized cells, which have different sets of proteins on opposite sides so that when one divides it can produce two different products. Polarization gives rise to asymmetric cell division, which produces one copy of the parent and a second cell that is programmed to turn into another cell type. Asymmetric cell division is the defining characteristic of a stem cell.
On rat brain samples, the researchers applied antibodies to identify proteins that may be involved in asymmetric cell division, and they found that polarization exists on the ependymal cells. "It couldn't have been a stronger signal or clearer message. We could see that the only cells undergoing asymmetric cell division were the ependymal cells," Gleason said.
Next, they gave a drug to induce cell division in the rats and examined their brains at intervals ranging from one to 28 days after the treatment. At each interval, they counted cells that were dividing in the ependymal layer. They found the most division at 28 days, when about one-quarter of the ependymal cells were dividing. Previous studies by researchers at other institutions were successful in getting only a few cells to divide in that layer.
"One interpretation of previous studies is there are scattered stem cells in the ependymal layer, and it is hard to locate them," Bryant said. "But we believe that all of the ependymal cells are stem cells, and that they all have the ability to be activated."
Researchers don't know yet what sparks cell division at the molecular level, but learning that process and how to control it could lead to a safe, effective stem cell therapy.
Fallon, psychiatry and human behavior professor, and researchers Magda Guerra and Jian-Chang Liu contributed to this study. All of the scientists are affiliated with the UCI Sue and Bill Gross Stem Cell Research Center.
Gleason's work is supported by a stem cell training grant from the California Institute for Regenerative Medicine. The UCI Office of Research, the Optical Biology Core in the Developmental Biology Center, a gift from the Joseph's Foundation, and the UC MEXUS-CONACYT Postdoctoral Research Program also
You sound distinctly unimpressed by this whereas I, on the other hand, find it really exciting!
The fact that the machinery of repair is already present in our brains and is functioning – however slowly and imperfectly – may mean that many, many of the processes that we were once going to have to overcome step by step could just be lying there waiting to be activated: like a line of dominoes waiting for the first push. I know it's never going to be that easy, but I'm very encouraged by this,
It is exciting, but the status quo is too slow. We need help and it may be on the way according to the research that you posted.
The work discussed by UCLA now being studied sounds a lot like the current trials going on at Neuren Pharmaceuticals. I have a great deal of faith in this approach.
My main negative reaction is that if left alone, as shown in the autopsies, the regeneration is too slow. Like Red Hair, I just had a recent birthday and am aware that the years are evaporating and that slow is not a "Make my day" kind of thought.
There is a story about a guy who had an 85% spinal cord injury that left him paralyzed 17 years ago that eventually got to doing triathalons through intense therapy! Rummerfield is his name.
My guess is that part of the issue in MS is that not only is the new nerve connection there, but the "alternative" is the preferred way of doing things from the brain's standpoint.
Ie if you could see me walk you'd see a woman with a marked limp; I lean far to the left to swing my right leg wide so it can clear the ground because it does not bend at the knee and I use a cane. This is how I walk now, it feels normal to me to do so and the nerve pathways that do it are well myelinated because they get used a lot.
If the nerves that used to be there had regenerated after a year but were weak, I'd still go back to my "normal" limping way of walking because that is strong and reliable nerve pathways now. And not only that, but the muscles involved are strong whereas the ones that had no nerve talk for that year are weak, shakey, and atrophied.
Even a golfer who has developed a bad habit swing of some kind has a hard time changing it to the "right" way, this is not wierd and special to MS stuff, itis normal body stuff.
My guess is that if we can activate these stem cells with some kind of brain derived neurotrophic factor or something AND if we can get good therapy we will see much more recovery than we think is possible right now.
Just for a little added positivity, it is known that kids can have half of the brain removed and still function well with nearly normal function; only one hand is unrecoverable. The difference is that they have some active factors stimulating the brain whereas adults have those same factors turned off. Those fators are being discovered all the time and I think we will be able to turn them on.
I can see no reason not to hope....
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I'm with you, Marie-mrhodes40 wrote:
I can see no reason not to hope....
Hope is the thing with feathers
That perches in the soul
And sings the tune without the words
And never stops at all.
And sweetest in the Gale is heard
And sore must be the storm
That could abash the little Bird
That kept so many warm.
I've heard it in the chillest land
And on the strangest Sea
Yet, never, in Extremity,
It asked a crumb of Me.
dx dual jugular vein stenosis (CCSVI) 4/09
Belief? They are resisting evidence because of a long-held belief?! I thought they were scientists.bromley wrote:Many scientists have resisted the increasing amount of evidence that shows regeneration of neurons in other areas of the brain, like the hippocampus, because of a long-held belief that the brain cannot regenerate.
There has been some research on meditation and neuroplasticity. Really exciting stuff if you're into that sort of thing.gwa wrote:Something needs to speed up the regeneration process because those of us with the progressive types only have continued downturns.
There are not too many things more frustrating than scientists who hang on to long-held beliefs because they have been that way for so long. These are likely the same researchers that have clung to the theory that MS is an auto-immune disease. They've had this idea for decades....and for decades the advancement of MS research has been nothing short of abysmal!!Belief? They are resisting evidence because of a long-held belief?! I thought they were scientists.
I suspect many people are quite happy with the status quo of Multiple Sclerosis research.
Thomas,Thomas wrote:Yes it's frustrating HarryZ, but we as patients must take some of the blame too. Why don't we DEMAND that neurologists and scientists come up with some answers? Why do we keep falling for the same old "OMG NEW GENE DISCOVERED! OMG SENSATIONAL MEDICAL BREAKTHROUGH COMING SOON!" year after year?
I suspect many people are quite happy with the status quo of Multiple Sclerosis research.
I can't count the number of MS information and research update seminars that I have attended over the years. Most were sponsored by the drug companies who had a neuro present the latest trial data for their "great promising drug" that showed potential for MS.
And at every seminar there were a few people who questioned how slowly MS research was going and why wasn't something different being done. The standard reply was always given.....be patient, we are just a few more years away from finding the answer.
Here I am, 30 years later, hearing the same thing now that I heard back then. And they STILL don't even know what causes MS!!
Bob,Stop the disease process and plasticity/healing process gets a chance to make some headway and ALL of the old MS "truisms" regarding not being able to make headway go out the window.
Anyone doubt that?
The human body does indeed have the ability to repair itself and we see this time and again. But with MS, a disease which has no known cause and certainly nothing remotely close to a cure, the body doesn't get a reprieve from the ongoing damaging attacks. The heavy duty immune system altering drugs that have been tried and tried on MS patients, at times give results that appear to be helping. But with the very nature of MS, the relapsing and remitting character of the disease really doesn't allow us to know if it's the drug that is doing something or whether the disease has done something on its own. Shake up one's immune system enough and you are going to see what looks like improvement but in the long run, the MS keeps on progressing.
I would really like to see some major accomplishment in treating MS in my lifetime but at the moment, I am not holding my breath.
Ahhhh... if it were so simple to stop the disease process. Revimune & campath are still in their early stages. Tovaxin is known to be reliant on someone having the MRTC's that go for their current "bait" so is not 100%.Lyon wrote:Stop the disease process and plasticity/healing process gets a chance to make some headway and ALL of the old MS "truisms" regarding not being able to make headway go out the window.
Only time will tell, but until then, sign me up!Lyon wrote:Anyone doubt that? One case does not make conclusive evidence, but situations like Raven's