You may have to stretch your imagination somewhat to see how the treatments talked about in today's article from sciencedaily.com (see link below) will eventually lead to simple treatments for our sort of neuropathy. However, you can follow the logic and because these scientists are dealing with worst-case-scenarios in terms of nerve damage, it is to be hoped that certain principles may eventually be applied to less traumatic neuropathies. In our case we'll have to wait for top-down solutions. Nerve damage caused by war or accident wounds is clearly of a different order than the neuropathy we suffer from with whole bodies but one would think that all progress in nerve repair, will eventually be relevant to us.
Step Forward in Effort to Regenerate Damaged Nerves
ScienceDaily (Feb. 21, 2012)
The carnage evident in disasters like car wrecks or wartime battles is oftentimes mirrored within the bodies of the people involved. A severe wound can leave blood vessels and nerves severed, bones broken, and cellular wreckage strewn throughout the body -- a debris field within the body itself.
It's scenes like this that neurosurgeon Jason Huang, M.D., confronts every day. Severe damage to nerves is one of the most challenging wounds to treat for Huang and colleagues. It's a type of wound suffered by people who are the victims of gunshots or stabbings, by those who have been involved in car accidents -- or by soldiers injured on the battlefield, like those whom Huang treated in Iraq.
Now, back in his university laboratory, Huang and his team have taken a step forward toward the goal of repairing nerves in such patients more effectively. In a paper published in the journal PLoS ONE, Huang and colleagues at the University of Rochester Medical Center report that a surprising set of cells may hold potential for nerve transplants.
In a study in rats, Huang's group found that dorsal root ganglion neurons, or DRG cells, help create thick, healthy nerves, without provoking unwanted attention from the immune system.
The finding is one step toward better treatment for the more than 350,000 patients each year in the United States who have serious injuries to their peripheral nerves. Huang's laboratory is one of a handful developing new technologies to treat such wounds.
"These are very serious injuries, and patients really suffer, many for a very long time," said Huang, associate professor of Neurosurgery and chief of Neurosurgery at Highland Hospital, an affiliate of the University of Rochester Medical Center. "There are a variety of options, but none of them is ideal.
"Our long-term goal is to grow living nerves in the laboratory, then transplant them into patients and cut down the amount of time it takes for those nerves to work," added Huang, whose project was funded by the National Institute of Neurological Disorders and Stroke and by the University of Rochester Medical Center.
For a damaged nerve to repair itself, the two disconnected but healthy portions of the nerve must somehow find each other through a maze of tissue and connect together. This happens naturally for a very small wound -- much like our skin grows back over a small cut -- but for some nerve injuries, the gap is simply too large, and the nerve won't grow back without intervention.
For surgeons like Huang, the preferred option is to transplant nerve tissue from elsewhere in the patient's own body -- for instance, a section of a nerve in the leg -- into the wounded area. The transplanted nerve serves as scaffolding, a guide of sorts for a new nerve to grow and bridge the gap. Since the tissue comes from the patient, the body accepts the new nerve and doesn't attack it.
But for many patients, this treatment isn't an option. They might have severe wounds to other parts of the body, so that extra nerve tissue isn't available. Alternatives can include a nerve transplant from a cadaver or an animal, but those bring other challenges, such as the lifelong need for powerful immunosuppressant drugs, and are rarely used.
One technology used by Huang and other neurosurgeons is the NeuraGen Nerve Guide, a hollow, absorbable collagen tube through which nerve fibers can grow and find each other. The technology is often used to repair nerve damage over short distances less than half an inch long.
In the PLoS One study, Huang's team compared several methods to try to bridge a nerve gap of about half an inch in rats. The team transplanted nerve cells from a different type of rat into the wound site and compared results when the NeuraGen technology was was used alone or when it was paired with DRG cells or with other cells known as Schwann cells.
After four months, the team found that the tubes equipped with either DRG or Schwann cells helped bring about healthier nerves. In addition, the DRG cells provoked less unwanted attention from the immune system than the Schwann cells, which attracted twice as many macrophages and more of the immune compound interferon gamma.
While both Schwann and DRG cells are known players in nerve regeneration, Schwann cells have been considered more often as potential partners in the nerve transplantation process, even though they pose considerable challenges because of the immune system's response to them.
"The conventional wisdom has been that Schwann cells play a critical role in the regenerative process," said Huang, who is a scientist in the Center for Neural Development and Disease. "While we know this is true, we have shown that DRG cells can play an important role also. We think DRG cells could be a rich resource for nerve regeneration."
In a related line of research, Huang along with colleagues in the laboratory of Douglas H. Smith, M.D. , at the University of Pennsylvania are creating DRG cells in the laboratory by stretching them, which coaxes them to grow about one inch every three weeks. The idea is to grow nerves several inches long in the laboratory, then transplant them into the patient, instead of waiting months after surgery for the nerve endings to travel that distance within the patient to ultimately hook up.
http://www.sciencedaily.com/releases/2012/02/120221125018.htm
Today's post from diabetescommunity.com (see link below) refers (as is so common) to diabetes, as if diabetes was the only cause of neuropathy. Experienced readers will know by now that any information regarding diabetic neuropathy also applies to many other forms of neuropathy unless there is specific reference to blood sugars. The article talks about a protein imaginatively called 'CCL2' which seems to be able to trigger regrowth in damaged nerve systems...in long-suffering mice. So it's another finding which is a long way off human application. However, it is extraordinary news that this protein has been identified as being so powerful. The suggestion is that this protein may only be effective in cases of nerve damage soon after injury (when the two ends of any damaged nerve or neuron are still 'alive') but reading more closely suggests that its effects may be more widespread than that and that it may be able to regenerate long damaged neurons. One to keep in the back of your mind for the future.
A signalling protein called CCL2 could enhance the regeneration of the peripheral nervous system, making it a potential treatment for diabetic neuropathy.
The research, which was conducted by researchers at Case Western Reserve University School of Medicine, indicates that C-C class chemokine 2 (CCL2) aids the repair of peripheral nerve cells following injury.
“We are excited about our findings because we had no reason to expect that just expressing the chemokine CCL2 would be enough to stimulate nerve regeneration,” said senior author Richard E. Zigmund, PhD, professor of Neurosciences and Pathology at Case Western Reserve University School of Medicine. “It is remarkable that just CCL2 should be so powerful.”
How does CCL2 work?
The positive effects of CCL2 are seen primarily in peripheral nerve clusters, which are also known as ganglia. There are two parts to every peripheral nerve cell: there is the “body” of the cell, and an axon, also known as a “tail”. The tail splits into two parts when it separates from the body, and these parts have different functions. One part picks up sensations around the body; the other relays that information to the brain and spinal cord.
Peripheral nerves are quite easily damaged, whether by cuts, fractures, or disease. Diabetes is one of the most common causes of peripheral nerve damage, and we call that diabetic neuropathy. CCL2 is useful when the nerves become damaged, because it sends out inflammatory immune cells known as macrophages, which allow new axons to grow.
Testing CCL2
To test the effects of CCL2 on damaged peripheral nerves, they gave mouse models a virus designed to increase their levels of the protein. Those mice had more macrophages and a higher neuron spread, which is a key part of nerve regeneration.
Another group of mice were engineered to express no CCL2. This group had very little nerve growth.
“We did the same experiments in another type of mouse and found the same correlation,” explained Zigmond. “If macrophages don’t come into the ganglia, then regeneration is substantially impeded. We found this true of sensory and sympathetic neurons. We concluded that there was a correlation between macrophage entry into ganglia and nerve regeneration.”
A new approach to inflammation?
The study indicates that the current clinical attitude towards inflammation might be flawed. At the moment, the tendency is to fight inflammation, but it may be more effective to allow a small amount of inflammation following an injury, so that the regeneration of neurons can be stimulated.
The findings are published in Experimental Neurology.
http://www.diabetescommunity.com/news/2016/01/ccl2-protein-helps-heal-damage-caused-diabetic-neuropathy-study-finds.html
Today's post from diabetesqld.org (see link below) is an article from an Australian website that reports on what could be the next big thing regarding neuropathy treatment. I know...I can hear you sighing...after so many 'next big things' that turn out to be false dawns, we tend to view new findings with some skepticism don't we? However, the science behind this one seems to be solid and although many more studies are needed (as always), the idea that non-invasive laser treatment may be able to repair damaged myelin sheaths (insulation around the nerves) is a very attractive one. Also encouraging; the Brazilian lab admits it doesn't know why this seems to work but they have some theories that time will either prove or disprove. It may be a question from a dumb onlooker but precisely where do you apply the laser treatment? The very nature of peripheral neuropathy means that the damaged nerves can be very hard to pin down and identify. Just because the pain is in the feet or hands, doesn't mean that the damage is there also. I guess we'll just have to wait and see but this is one of those research discoveries you hope will turn out to be true and workable for us long-term sufferers.
31 March 2017 / Recent studies at the University of São Paulo's Biomedical Science Institute (ICB-USP) in Brazil shows low-level laser therapy to be a non-invasive and effective alternative for treating neuropathic pain, a chronic condition caused by nerve damage, spinal cord injury or diseases such as diabetes.
The treatment in a model of diabetic neuropathy, one of the most common chronic and incapacitating complications of diabetes, was tested. Neuropathic pain in diabetes occurs when the disease is not properly controlled and excessive amounts of blood sugar cause oxidation of the myelin sheath, damaging the structure of peripheral nerves. As well as causing pain, this degenerative process impairs communication among neurons and can even lead to amputation of the lower limbs.
"We tested laser therapy in different rat neuropathy models, and behavioral responses improved in all of them," Professor Marucia Chacur, the principal investigator, said. "One of the beneficial effects observed was myelin sheath recovery. The myelin sheath is a lipid layer that covers the axon and acts as electrical insulation to assist nerve impulse propagation."
With the aid of a transmission electron microscope, the researchers found that as diabetes progressed, the structure of the sciatic nerve's myelin sheath changed. After four sessions of the treatment, however, the myelin had almost completely recovered.
"The condition of the nerve practically returned to baseline levels after treatment. We're now continuing the study by analyzing protein expression and the release of inflammatory cytokines to understand exactly what's happening," Chacur said.
In a second study, treatment focused on the sciatic nerve, and found that astrocytes - star-shaped cells that play an active role in brain function and inflammatory responses - were the first type of cell to migrate to the site of a nerve injury or inflammatory process. These cells release several inflammatory mediators, which in turn trigger the release of other inflammatory substances.
"We believe the laser curtails this chain reaction as if it were anti-inflammatory medication, by reducing the migration of astrocytes to the site of the injury," Chacur said.
The third model used to test low-level laser therapy focused on orofacial pain, involving the inferior alveolar nerve, one of the branches of the trigeminal nerve responsible for innervating the face. Phototherapy started two days after injury and improvement was observed after two sessions.
"We set out to understand the mechanisms and mediators involved because we believed phototherapy could be used in association with pharmacological treatment because it acts via a different pathway. In this way, it may be possible to reduce the drug dose and mitigate the systemic effects of the treatment," Chacur said.
The results suggest that all three models of neuropathic pain studied share a common mechanism involving myelin sheath regeneration and reduced astrocyte migration to the site of the lesion, she added.
"Evidence in the literature also suggests an effect on mitochondria. The laser apparently facilitates the flow of calcium in these organelles, boosting production of ATP [adenosine triphosphate, the body's cellular fuel] and leading to enhanced healing as well as the release of mediators that assist remodeling. In future studies, we plan to investigate this effect on mitochondria more thoroughly," Chacur concluded.
http://www.diabetesqld.org.au/media-centre/2017/march/neuropathic-pain-science-says-lasers-can-help.aspx
