3 D Digital Print Outs To Restore Damaged Nerves

Today's post from the always-reliable, sciencedaily.com (see link below) looks at the potential use of 3-D printed, custom silicone guides implanted with biochemical cues to help nerve regeneration after injury. Now this isn't the replacing of damaged nerves caused by any number of factors that we know of as being neuropathy (maybe later) but it is a major breakthrough with enormous potential. It's also not printing out digital 'plastic 'nerves' that could function as real ones - it's the placing of the right 'stimuli' between damaged nerve ends to encourage them to rejoin naturally. Of course, at the moment, experiments have only taken place on rats and who knows how long it will be before damaged nerves are regenerated in this way in humans but everybody living with neuropathy will be excited at the prospect of having a sort of, 'nerve transplant' in the same way that other organs of the body are currently transplanted. Science fiction? Not any more!

3-D printed guide helps regrow complex nerves after injury 
Date:September 18, 2015 Source:University of Minnesota

Summary:

Scientists have developed a first-of-its-kind, 3-D printed guide that helps regrow both the sensory and motor functions of complex nerves after injury. The groundbreaking research has the potential to help more than 200,000 people annually who experience nerve injuries or disease.


This is a 3-D printed nerve regeneration pathway implanted in a rat helped to improve walking in 10 to 12 weeks after implantation.
Credit: University of Minnesota College of Science and Engineering

A national team of researchers has developed a first-of-its-kind, 3D-printed guide that helps regrow both the sensory and motor functions of complex nerves after injury. The groundbreaking research has the potential to help more than 200,000 people annually who experience nerve injuries or disease.

Collaborators on the project are from the University of Minnesota, Virginia Tech, University of Maryland, Princeton University, and Johns Hopkins University.

Nerve regeneration is a complex process. Because of this complexity, regrowth of nerves after injury or disease is very rare, according to the Mayo Clinic. Nerve damage is often permanent. Advanced 3D printing methods may now be the solution.

In a new study, published today in the journal Advanced Functional Materials, researchers used a combination of 3D imaging and 3D printing techniques to create a custom silicone guide implanted with biochemical cues to help nerve regeneration. The guide's effectiveness was tested in the lab using rats.

To achieve their results, researchers used a 3D scanner to reverse engineer the structure of a rat's sciatic nerve. They then used a specialized, custom-built 3D printer to print a guide for regeneration. Incorporated into the guide were 3D-printed chemical cues to promote both motor and sensory nerve regeneration. The guide was then implanted into the rat by surgically grafting it to the cut ends of the nerve. Within about 10 to 12 weeks, the rat's ability to walk again was improved.

"This represents an important proof of concept of the 3D printing of custom nerve guides for the regeneration of complex nerve injuries," said University of Minnesota mechanical engineering professor Michael McAlpine, the study's lead researcher. "Someday we hope that we could have a 3D scanner and printer right at the hospital to create custom nerve guides right on site to restore nerve function."

Scanning and printing takes about an hour, but the body needs several weeks to regrow the nerves. McAlpine said previous studies have shown regrowth of linear nerves, but this is the first time a study has shown the creation of a custom guide for regrowth of a complex nerve like the Y-shaped sciatic nerve that has both sensory and motor branches.

"The exciting next step would be to implant these guides in humans rather than rats," McAlpine said. In cases where a nerve is unavailable for scanning, McAlpine said there could someday be a "library" of scanned nerves from other people or cadavers that hospitals could use to create closely matched 3D-printed guides for patients.

In addition to McAlpine, major contributors to the research team include Blake N. Johnson, Virginia Tech; Xiaofeng Jia, University of Maryland and Johns Hopkins University; and Karen Z. Lancaster, Esteban Engel, and Lynn W. Enquist, Princeton University.

This research was funded by grants from the National Institutes of Health, the Defense Advanced Research Projects Agency, the Maryland Stem Cell Research Fund, and the Grand Challenges Program at Princeton University.

To read more about the study entitled "3D Printed Anatomical Nerve Regeneration Pathways," visit the Advanced Functional Materials website.

Story Source:

The above post is reprinted from materials provided by University of Minnesota. Note: Materials may be edited for content and length.

Journal Reference: 
 
Blake N. Johnson, Karen Z. Lancaster, Gehua Zhen, Junyun He, Maneesh K. Gupta, Yong Lin Kong, Esteban A. Engel, Kellin D. Krick, Alex Ju, Fanben Meng, Lynn W. Enquist, Xiaofeng Jia, Michael C. McAlpine. 3D Printed Anatomical Nerve Regeneration Pathways. Advanced Functional Materials, 2015; DOI: 10.1002/adfm.201501760

http://www.sciencedaily.com/releases/2015/09/150918105030.htm

Neuropathy And Vitamin D

Today's post from neuropathydr.com (see link below) follows up on recent articles about the importance of getting enough (but not too much!) vitamin D in our daily diets. It's especially important for people susceptible to or living with neuropathy, as shortage of vitamin D can affect the regeneration of damaged nerves. This short article is worth a read but always consult with your doctor before embarking on a course of Vitamin D - it can be toxic at very high levels so getting the dosage right is important.

Vitamin D and Neuropathy?
Posted by john on September 12, 2013
 
Vitamin D is necessary for the body to manufacture some key neurotropic factors.

Yes, and this essential vitamin has a role in many other disorders too. Vitamin D is a key nutrient, responsible for many essential functions in human body.

What’s the Connection?

Perhaps the most significant functions are maintenance of bone mass and a powerful immune system. The more recent research suggests many additional roles for this key nutrient. We now know that when Vitamin D levels are low, widespread aches and pains plus more illnesses like flus and colds are common.

Yes, and maybe even neuropathy, both directly and indirectly.

Regarding infections, some researchers suggest we should be heading out vitamin D tablets as opposed to flu shots as they probably would be so much more effective, with minimal side effects.

But that’s another story for another time.

The neuropathy Vitamin D connection probably is because Vitamin D is necessary for the body to manufacture some key neurotropic factors.

Neurotropins as they are often called are substances produced by the body to help nerves repair, and whenever possible regenerate.

There are a number different things that can influence your own neurotropin production, including key nutrition components and therapies like low-frequency nerve stimulation.

In fact, the research is so significant here I am “bullish” on neurostimulator kits being tried for most neuropathy and pain patients.

This is why our homecare kits have become a very popular choice and work well the vast majority of the time. If you are new to Beating Neuropathy can find these at http://neuropathydr.com/homecare

So how much vitamin D is enough?

Well, United States says around 600 international units per day is fine, but European countries recommend levels much higher, on the order of a few thousand international units per day for most healthy adults.

So who is correct? I would definitely side with Europeans on this because research supports that most people do not get nearly enough vitamin D either from their diet, or sunlight exposure.

Personally, I recommend a minimum of 2500 units of supplemental Vitamin D per day combined with The NeuropathyDR Diet.

There are unfortunately no good plant sources of active vitamin D. (cholecaliferol).

The best dietary sources of vitamin D come from fish and fish oils.

But the most important advice I will leave you with today is to have your baseline levels of vitamin D checked, you and your healthcare providers must then determine the most optimum dosage for YOU!

Retest after the first 90 days to make sure your body is absorbing this key neuropathy nutrient properly.

You also need to be very careful because vitamin D can be toxic in very large amounts.

To learn more, check back with us frequently as we will update you periodically as the research indicates.

http://neuropathydr.com/vitamin-d-and-neuropathy/

Intra Muscular Vitamin D Injections Reduce Neuropathy Symptoms

Today's post from vitamindcouncil.org (see link below) makes some remarkable claims about the benefits of a single, high-dosage injection of vitamin D for neuropathy patients. The results were seen after some weeks and had no effect on the disability of a patient but definitely on the severity of their symptoms. Personally, I find it an encouraging research but it definitely needs some significant follow-up to confirm its conclusions. The injections were intra-muscular and therefore administered by a doctor or medical professional, which may be a good thing, to dissuade people from rushing to the supplement store to swallow 600,000 IU of vitamin D in pill form in one go! Vitamin D supplementation has been a buzz therapy among the neuropathy communities for some time now but most doctors will agree that vitamin D supplementation is only really necessary if there is proven vitamin D deficiency. The word has it that it is certainly beneficial for nerve health but you need to do more of your own research and consult with a trusted medical professional before embarking on a self-help course of vitamin D. Most articles place an emphasis on diabetes-related neuropathy patients but as we all know by now, that's only because the vast majority of neuropathy sufferers come from the diabetic community. Most information regarding neuropathy applies to the condition irrespective of its cause. More articles can be found by using the search button to the right of this blog.

Research finds vitamin D to be a safe and effective treatment for painful diabetic neuropathy
Posted on April 11, 2016 by Amber Tovey

A new study published in the journal BMJ Open Diabetes Research and Care discovered that treatment with a single intramuscular dose of 600,000 IU of vitamin D in patients with painful diabetic neuropathy caused significant reductions in symptoms.

Diabetic neuropathy is a type of nerve disorder that can occur if a person has diabetes. High blood sugar can injure nerves throughout the body, but diabetic neuropathy most commonly affects nerves in the legs and feet. It often causes pain and numbness in the extremities, but may also cause problems in the gastrointestinal tract, urinary tract, blood vessels and heart.

Approximately 21% of the population is affected by painful diabetic neuropathy. Treatments for diabetic neuropathy are limited. The therapeutic effectiveness for all medications is at best near 50% pain relief. In addition, most of the medications are accompanied by unwanted side effects. This has left the medical community searching for new treatments.

A previous study suggested vitamin D supplementation may help treat diabetic neuropathy. The researchers found that weekly vitamin D supplementation of 50,000 IU for 8 weeks reduced symptoms but not disability. In an effort to confirm the treatment effect of vitamin D on diabetic neuropathy, researchers recently conducted a prospective open-labeled trial in Pakistan.

A total of 143 patients with type 1 or type 2 diabetes were included in the study. All patients received a single intramuscular dose of 600,000 IU of vitamin D3.

Pain was assessed using three different questionnaires: The Douleur Neuropathique 4 (DN4), total McGill pain and Short Form McGill Pain Questionnaire (SFMPQ). The researchers wanted to compare pain severity before and after the administration of the vitamin D injection. Here is what they found:
Average vitamin D levels increased from 31.7 ng/ml at baseline to 46.2 ng/ml at week 20.
Total McGill pain score, DN4 and SFMPQ significantly decreased after vitamin D administration (p is less than 0.001).

The researchers concluded,

“The administration of 600 000 IU of vitamin D results in a modest but significant increase in 25(OH)D levels measured at 20 weeks. This improvement in 25(OH)D levels was associated with an improvement in several independent measures of PDN, which became significant approximately 10 weeks after administration of vitamin D.”

The researchers noted that the average vitamin D levels of the patients at baseline was much higher than previous studies, indicating that a proportion had likely received vitamin D supplementation from their primary physician previously. This shows vitamin D supplementation has become a more widely accepted practice for diabetic patients.

Future studies should follow a randomized controlled trial design and use a daily dosage regimen.

Citation

Tovey, A.; Cannell, JJ. Research finds vitamin D to be a safe and effective treatment for painful diabetic neuropathy. The Vitamin D Council Blog ; Newsletter, 2016.

https://www.vitamindcouncil.org/blog/research-finds-vitamin-d-to-be-a-safe-and-effective-treatment-for-painful-diabetic-neuropathy/

A GLIMPOSE IN TO THE 3 D BRAIN HOW MEMORIES FORM

People who wish to know how memory works are forced to take a glimpse into the brain. They can now do so without bloodshed: RUB researchers have developed a new method for creating 3D models of memory-relevant brain structures. They published their results in the journalFrontiers in Neuroanatomy.

The way neurons are interconnected in the brain is very complicated. This holds especially true for the cells of the hippocampus. It is one of the oldest brain regions and its form resembles a see horse (hippocampus in Latin). The hippocampus enables us to navigate space securely and to form personal memories. So far, the anatomic knowledge of the networks inside the hippocampus and its connection to the rest of the brain has left scientists guessing which information arrived where and when.

Signals spread through the brain

Accordingly, Dr Martin Pyka and his colleagues from the Mercator Research Group have developed a method which facilitates the reconstruction of the brain's anatomic data as a 3D model on the computer. This approach is quite unique, because it enables automatic calculation of the neural interconnection on the basis of their position inside the space and their projection directions. Biologically feasible network structures can thus be generated more easily than it used to be the case with the method available to date.

Deploying 3D models, the researchers use this technique to monitor the way neural signals spread throughout the network time-wise. They have, for example, found evidence that the hippocampus' form and size could explain why neurons in those networks fire in certain frequencies.

Information become memories

In future, this method may help us understand how animals, for example, combine various information to form memories within the hippocampus, in order to memorise food sources or dangers and to remember them in certain situations.

MODIFIED VITAMIN D SHOW PROMISE AS TREATMENT FOR PANCREATIC CANCER

A synthetic derivative of vitamin D was found by Salk Institute researchers to collapse the barrier of cells shielding pancreatic tumors, making this seemingly impenetrable cancer much more susceptible to therapeutic drugs.

The discovery has led to human trials for pancreatic cancer, even in advance of its publication today in the journal Cell. By attacking a wound repair mechanism called fibrosis, the findings may also have implications for other tough-to-treat tumors, such as lung, kidney and liver cancer.

"While the success of this drug in humans with pancreatic cancer is still unclear, the findings in animal studies were strong, raising hope that ongoing clinical trials will give people with this terrible disease hope for a truly new type of therapy," says Ronald Evans, director of Salk's Gene Expression Laboratory and senior author of the new paper.

Pancreatic cancer is one of the deadliest forms of cancer, a fact highlighted in recent years by the deaths of well-known figures such as Steve Jobs and Patrick Swayze. About 46,000 people are diagnosed in the United States each year and about 40,000 people die from the disease, according to the National Institutes of Health.

"For pancreatic cancer, the five-year survival rate is the lowest of all cancers," says Evans, holder of Salk's March of Dimes Chair and a Howard Hughes Medical Institute investigator. "Part of the problem is that the science of pancreatic cancer and its renowned resistance to therapy has not been understood and that's why the work that we're doing is so important."

Evans and his colleagues knew that the ability of the pancreatic tumor to communicate with nearby cells -- called the tumor microenvironment -- is key to its growth. Tumor cells send out signals that make the microenvironment inflamed and dense; this "living shield" around a tumor not only helps the cancer grow, but blocks the access of immune cells and chemotherapeutic drugs, making the cancer particularly hard to treat.

Evans -- in collaboration with researchers around the country involved in an interdisciplinary initiative supported by Stand Up to Cancer -- wanted to figure out how to restore this inflamed microenvironment to its normal or "quiescent" state and weaken the wall around the tumor.

"There was evidence that the activation of the microenvironment was theoretically reversible, but nobody knew exactly what was responsible for the activation, making it hard to turn off," says Salk postdoctoral research fellow Mara Sherman, first author of the new paper.

Sherman, Evans and their collaborators focused their attention on one component of this wall: pancreatic stellate cells, which usually respond to small injuries by briefly switching to an activated state, spurring new cell growth. In the case of cancer, however, the stellate cells near a tumor -- in response to signals from the tumor -- are constantly turned on. This chronic activation of the stellate cells provides the tumor cells with extra growth factors and therefore helps them proliferate, but also forms a wall-like barrier around the tumor that protects it from chemotherapeutics and other cancer-fighting drugs.

In 2013, Evans' group discovered that stellate cells in the liver could be inactivated by a chemically modified form of vitamin D. They wondered whether the same could hold true in the pancreas, despite the fact the vitamin D receptor was not thought to be present in pancreatic tissue.

But indeed, when the group of researchers examined the differences between activated and inactivated stellate cells in the pancreas, they found that activated stellate cells near a tumor had high levels of the vitamin D receptor. And when the researchers then added modified vitamin D to activated stellate cells the cells quickly reverted back to a healthy, inactivated state, stopping production of signals that spur growth and inflammation.

"This was a big surprise because vitamin D has been tried multiple times as a therapy for pancreatic cancer and never worked," says Evans.

It turns out that activated stellate cells rapidly break down normal vitamin D, preventing the vitamin from binding to the receptor, Evans explains. But systematic analysis of vitamin D analogues allowed the team to discover a modified form of vitamin D that is more stable, resilient and effective in vitro.

To see whether this new vitamin D-like compound could halt the growth of a tumor, Evans and the team next studied its effectiveness in mice. The researchers found that combining the drug with existing chemotherapeutics gave a 50 percent increase in lifespan compared to chemotherapy alone.

"It's really remarkable considering that vitamin D itself is not attacking the cancer cells," says Michael Downes, a senior staff scientist at Salk and co-corresponding author of the new work. "It's changing the environment to a more favorable setting needed for the chemotherapy drugs to work."

Studies have shown that people deficient in vitamin D are more likely to develop pancreatic cancer. Based on the new results, Evans thinks that healthy levels of vitamin D may help keep vitamin D receptor signaling in stellate cells normal and squash a cancer's growth -- at least until a tumor itself forces the stellate cells to "turn on."

"Recently, other research groups have explored the idea of destroying the microenvironment altogether to weaken a tumor," says Downes. "Our approach is very different. Instead of destroying, we simply want to reprogram the tumor microenvironment to a healthy state. This has the dual effects of delivering more drugs to the tumor as well as replenishing the tissue with normal stellate cells."

Evans group has already teamed up with clinicians at the University of Pennsylvania to launch a clinical trial testing the effectiveness of using their vitamin D-like drug in cancer patients before pancreatic surgery. "Previous trials with vitamin D failed because they didn't understand the need for a special form of vitamin D and that for pancreatic cancer it must be used in combination with chemotoxic drugs," Evans says. "So, by re-thinking the problem, have been able to open up a new route to the treatment of pancreatic cancer and, looking forward, hopefully other diseases as well."