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Non-surgical procedure repairs severed nerves in minutes

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February 7, 2012

U.S. researchers have developed a nonsurgical technique to repair severed nerves in minute...

U.S. researchers have developed a nonsurgical technique to repair severed nerves in minutes instead of months (Image: Shutterstock)

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Professor George Bittner and his colleagues at the University of Texas at Austin Center for Neuroscience have developed a simple and inexpensive procedure to quickly repair severed peripheral nerves.

The team took advantage of a mechanism similar to that which permits many invertebrates to regenerate and repair nerve damage. The new procedure, based on timely application of common chemicals to the severed nerve ends, could help patients to recover nearly full function in days or weeks.

Peripheral nerves connect the central nervous system to the muscles and sensory organs. Nerves contain a bundle of cylindrical sheaths called axons, within which reside individual nerve cells. The axons are surrounded by Schwann cells which coat the axons with myelin.

Trauma to peripheral nerves is relatively common. A nerve that has been damaged by pressure or stretching generally has a severed nerve fiber inside an intact axon. A severed nerve occurs when both the nerve fiber and the axon are cut in two. Either injury can prevent muscles from working and result in loss of feeling from the area of the body served by that nerve, often for years thereafter.

Why is nerve repair in mammals such a slow process?

When a nerve fiber breaks within its axon, the broken end of the nerve fiber which is no longer connected to the central nervous system dies, leaving an empty axonal tube from the point of injury. The nerve fiber will slowly grow within the empty tube, at a rate of about an inch per month. Thus, even minor nerve injuries commonly take months or years to heal. Even then the regrown nerves rarely meet up perfectly with the original muscles and sensory organs, so that a significant amount of function is permanently lost.

In what is known as Grade V neurotmesis, the axon is severed along with the nerve fiber. The growth of the regenerating nerve fiber is not constrained, and can form a twisted ball of nerve fiber at the cut in the axon. Such nerve scars are called neuroma, and can be extremely painful. Recovery from Grade V nerve injury is never rapid, usually taking months or years for even partial recovery.

In current medical practice, a cut nerve is repaired by using microsutures to reconnect the cut ends of the axon in an extraordinarily delicate operation (imagine sewing together two limp strands of angel hair pasta).

The object is to provide a continuous axon to guide the regrowth of the nerve fiber. Again, the regrowth process takes months or years to be completed, and typically the function of the original nerve will remain impaired.

A new approach

Professor Bittner's team had discovered earlier that when a plasma membrane is damaged, a calcium-mediated healing mechanism starts to draw small vesicles toward the site of the injury. Vesicles are small sacks made of lipid membranes which provide the material needed to repair an injured plasma membrane. However, when the vesicles are attracted to the site of a severed axon, both ends of the axon are sealed off by this repair mechanism, preventing regrowth of the nerve.

To avoid this problem, the first step of the Texas group's nerve repair procedure is to bathe the area of the severed nerve with a calcium-free saline solution. By removing calcium from the injured axons, premature healing of the axon ends by this vesicle-based repair mechanism is prevented and even reversed. The damaged axons remain open, and can more easily be reattached. The calcium-free solution also contains antioxidants (e.g., methylene blue) to prevent degenerative changes in the axon and nerve.

In standard methods, the two ends of the severed axon would be reattached surgically. In contrast, Bittner's procedure does not require such difficult microsurgery. Instead, the severed ends of the axon are pulled to within a micron of each other, whereupon a small amount of a solution containing polyethylene glycol (PEG) is injected. The PEG removes water from the axonal membranes, allowing the plasma membranes to merge together, thereby healing the axon.

At the same time, the nerve fibers are brought into close enough proximity that they receive chemical messengers from each other making them believe they are still whole, thereby preventing the death of the disconnected nerve fiber. The severed nerve fibers can then grow together in a short period of time and with relatively good fidelity to the original connectivity of the nerve fibers.

The final step of the procedure is to inject the area with a calcium-rich saline solution, which restarts the vesicle-based repair mechanism, thereby repairing any residual damage to the axonal membrane. At this point, the nerve is structurally repaired, and use of the affected area begins to return within a few hours.

Indeed, tests of Bittner's procedure on rats have indicated an amazing level of success. The sciatic nerve of the rats was cleanly severed, resulting in paralysis of the affected limb.

Within minutes of awaking from Bittner's procedure, many of the rats were immediately able to move the limb containing the severed nerve. The normal function of the limb was partially restored within a few days, and 80-90% of the pre-injury function was restored within two to four weeks. Control rats subjected to sciatic nerve cutting followed by a sham procedure permanently lost nearly all (95-98%) function in the affected limb.

The chemicals used in Bittner's procedure are common and well understood in interaction with the human body. PEG is on the FDA's GRAS (generally recognized as safe) list, and methylene blue is an aromatic dye used for staining histological samples, as well as in fabric stains and paints. Because of this, there is no clear obstacle to beginning human clinical trials of the procedure. Indeed, teams at Harvard Medical School and Vanderbilt Medical School and Hospitals are currently conducting studies aimed at gaining approval for such trials. While the procedure developed by Bittner's group will not apply to the central nervous system or spinal cord injuries, the procedure offers hope to people whose futures include accidents involving damaged nerves.

Sources: University of Texas, News in Physiological Sciences

About the Author
Brian Dodson From an early age Brian wanted to become a scientist. He did, earning a Ph.D. in physics and embarking on an R&D career which has recently broken the 40th anniversary. What he didn't expect was that along the way he would become a patent agent, a rocket scientist, a gourmet cook, a biotech entrepreneur, an opera tenor and a science writer.   All articles by Brian Dodson
16 Comments

This method could work within the CNS. Try it.

The reason that no regeneration of CNS fibers is possible is because of the circulating adult proteins. Use fetal circulation for damaged nerves and that should hook it back up readily. (Yes, I have 1000 X's your I.Q.)

TogetherinParis
8th February, 2012 @ 12:09 am PST

I love elegant solutions. this one is great!

William Moran
8th February, 2012 @ 04:59 am PST

Non-surgical??? how do they propose to bring the nerve endings together without surgery? how do they bathe the area with those chemicals without cutting?

i'm not decrying the procedure, just the wording of the article.

notarichman
8th February, 2012 @ 07:30 am PST

@TogetherinParis And not a quarter of the charisma of a normal person. ;-P

John Flower
8th February, 2012 @ 07:48 am PST

I think they mean without suturing the nerve ends together (sewing limp angel-hair pasta) - I could see this being done with nearly only injections. . .

socalboomer
8th February, 2012 @ 12:31 pm PST

How does one sign up.. for the human trial??

Cherei J McCarter
8th February, 2012 @ 02:08 pm PST

I for one cannot wait for this procedure to happen as I have a dead foot from a car running a stop sign and cleaning me up on my harley and basic destroying my leg from the knee to the toes and all feeling so any one that knocks this method should walk a mile in my shoes and then they may discover that I cannot walk very far at all without crutches .

From a downed biker

Downed Biker
8th February, 2012 @ 07:08 pm PST

A modified version of methylene blue was successfully used to completely stop the progression of Alzheimer's in several patients in a trial. However it did not repair any of the damage.

When their brains were examined after death, there was no trace of amyloid plaque. The methylene blue had cleaned it out.

So why isn't this treatment being used? Some of the people in the test group had adverse reactions.

Why not develop a test to see who would and wouldn't have the bad reaction so that people with Alzheimer's and can take the stuff can have their disease stopped early on?

But that's how so much stuff is done in medicine, can't use it unless it's 100% absolutely safe.

Gregg Eshelman
9th February, 2012 @ 12:47 am PST

Anyone have any idea when this surgery will be avaliable?

Gunnar Young
6th July, 2012 @ 06:37 pm PDT

So my friend is at Froedert in WI with a burst fracture to T11 they repaired the vertebrae and have said that his spinal cord is not completely severed but they tell him do not expect to walk again.. could this procedure be something to bring up? The initial injury was 11 days ago.

Richard Trudeau
3rd August, 2012 @ 04:25 am PDT

IM YOUR HUCKLEBERRY! please tell me how i can be a Guinea pig !

Leland Walker
13th April, 2013 @ 09:29 pm PDT

I had a spinal injury 16 years ago. Flying accident.

I was told I had a complete injury 4 weeks later and would never walk again! I did not believe that! Two weeks after that I could move my left quad. Then slowly more recovery and took my first steps 6 months after my accident.

I have recovered such extent that I only need canes to walk. Gave up using a wheelchair 3 years after my accident.

The downside to recovery is that I get pain pretty much every second day on the new nerves which are recovering. Small price to pay for the gains I am getting. I think nerve recovery is one thing and then you need to exercise to grow those atrophied muscles again. So start exercising before the magic pill! I do not believe in pills as I do not take any painkillers either!

Life is pretty good!

Henry Van Campa
17th May, 2013 @ 11:20 pm PDT

@Henry Van Campa-one of my frnd has c1-c2 avm hemorraghe that make him quadriplegic. Bt with physiotherapy and medicine he had his motor power back. Now he dont have proper sensation. As you are experienced in this, kindly suggest and help my frnd.

Geetika Devi
16th June, 2013 @ 10:48 pm PDT

How do I get this?? I suffered a brain injury along with stroke 4 years ago, and I'm beyond intrigued by this! Who can give me more information??

Elise Kathleen Noel
16th July, 2013 @ 03:29 pm PDT

Hi,

My brother met with an accident 3 years back. He got a bad hit with a truck on his forehead with a huge force which resulted his neck to push back all of a sudden and lead to Axonal Nerve Injury. He was on Ventilator for 10 days and after that he opened his eyes..But he was unable to speak or recognize any of our acts(still in coma with his eyes opened).Then slowly he started recognizing people after 3 months but doctor said it is an Grade 4 Axonal Nerve Injury, and it will take long time to recover. He is still unable to walk properly.He lost his balance. Initially we saw very fast recovery like standing,sitting and walking.But after an year, that recovery is constant..

Can any one please suggest me the hospitals or kind of treatments which heals the Axonal Nerve Injury-Grade 4 completely and what is the chance of complete cure..And how much time it will take for the patient to become normal.???

Please suggest the needful..

Ajay2421
3rd October, 2013 @ 11:36 am PDT

While I think that such research and developments are important, it is crucially important to respond on these sites as well. If the authors of the articles are not the points of contact, provide who is. People are hurting and searching for answers. True information without communication fosters depression and most needing this information are already at that point. Understand that we all need to be updated with all areas of medical possibility, but with no real opportunity to see if these efforts are feasible for those of us that have hope...it is a mute point and I would rather keep it that way. Continue to educate...but provide all we might need to research on our own. It's a glimmer...but its a start.

Pilar Garner
21st August, 2014 @ 10:29 am PDT
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