Rodent of the Week: Axons regenerate long after injury

[Christopher]

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Rodent of the Week: Axons regenerate long after injury

October 30, 2009 | 1:00 pm

Rodent Scientists have been working for more than a decade on methods to treat spinal cord injuries by attempting to regrow injured nerves. Some success has been achieved in animals that are treated immediately after the injury.

However, new research shows it's possible to coax the regeneration of nerve axons in rats as long as a year after injury. Axons are the part of the nerve that carries signals away from the nerve body. In the experiment, researchers were able to stimulate the growth of axons in the damaged part of the spinal cord and somewhat beyond the site.

It's difficult to get injured axons to grow because of scar tissue at the injury site, inflammation and chemical processes that inhibit the growth. Thus, the treatment was dependent on a complex and sophisticated process that included a cellular bridge to the injury site, a nervous-system growth factor to guide axons to the correct target and a stimulus to the injured neurons that turns on genes to promote growth.

Using this formula, researchers were able to demonstrate successful regeneration of axons. Rats that did not receive the full combination treatment did not exhibit growth.

"The good news is that when axons have been cut due to spinal cord injury, they can be coaxed to regenerate if a combination of treatments is applied," the lead author of the study, Dr. Mark Tuszynski of UC San Diego, said in a news release. "The chronically injured axon is not dead.

"While the regenerating axons grow for relatively short distances, even this degree of growth could be useful. For example, restoration of nerve function even one level below an injury in the neck might improve movement of a wrist or hand, providing greater quality of life or independence."

The study is published in the journal Neuron http://www.cell.com/neuron/abstract/S08 ... %2900698-9.

- Shari Roan

[Christopher]

http://abcnews.go.com/Health/WellnessNe ... id=8939148

Rat Study Shows Promise in Eventual Paralysis Treatment
Delayed Treatment of Spinal Injuries Could One Day Be Practical, Researchers Say
By DR. JUDY NEE
ABC News Medical Unit
Oct. 29, 2009


Ten or fifteen years ago, if any one of the 6 million people estimated to be living with paralysis searched for treatment, they would likely have found hope in short supply. More often than not, they were told their condition was permanent.

Research since then has shown that if the damage from spinal cord injuries is dealt with immediately, there may be hope that some patients can avoid total paralysis. But if treatment is delayed, the chances of success quickly dwindle.

Now, in an unprecedented new study from the University of California, San Diego, published Wednesday in the journal Neuron, researchers say they were able to regenerate nerve cells up to 15 months after a spinal cord injury.

"All studies in the past have been right after the injury, but with a quarter million [people with chronic spinal injury], we needed a study that looked at re-growth one year after," said Dr. Mark H. Tuszynski, director of the Center for Neural Repair at UCSD and one of the authors of the study. "We found one can achieve this at impressive delays."

Only Preliminary, Only in Rats So Far

But like much of the other current paralysis research, this finding is only preliminary. The study was conducted only in rats -- so it is hard to say how it may apply to people. And while the data is promising, doctors specializing in spinal cord injury caution that this is at least a decade away from being rolled out as therapy for humans.

Moreover, the trial at hand was largely a test run; the nerves that the researchers regenerated in the rats were picked because they would be the most easy to study and simplest to re-grow. Additionally, while the nerves that were studied re-grew, they did not connect to the brain in the way needed to restore sensory or motor function.

Can a Damaged Spinal Cord be Repaired?

"None of the animals had any improvement in neurological function," said Dr. Arthur Jenkins, co-director of Mt. Sinai Hospital's Neurosurgical Spine Program.

Other neurology experts agreed.

"This is still an animal model of an injury far from clinical trials," said Dr. Peter Konrad, director of functional neurosurgery at Vanderbilt University. We cannot tell whether this re-growth will actually make a patient walk again or regain feeling."

From Mice to Men? Experts Remain Hopeful

Still, those in the field said this is one step in what may one day be a hopeful future for chronic spinal cord injury patients. Dr. Edward Hall, director of the Spinal Cord and Brain Injury Research Center at the University of Kentucky in Lexington, calls it a "landmark study that is one of the first to investigate a combination therapeutic approach aimed at improving regeneration of spinal cord fibers across a spinal cord lesion."

"It's unbelievable," said Dr. James Harrop, associate professor of neurological surgery at Thomas Jefferson University Hospital. "You usually have all this scar, and the neurons can't get through the scar... Your body is sending signals so that it won't get better."

That scar tissue was thought to be one of many factors researchers were up against in nerve regeneration if months passed after the injury. Researchers in the study used a "triple combination therapy": they combined the injured nerve cells, placed a "bridge" made of stem cells at the injured spot, and flooded the area around the spinal cord with chemicals naturally found in the body that help tissues grow.

By using combination therapy, as neurology expert Dr. Naomi Kleitman noted, "[One of the] really significant finding[s] here is that the nerve fibers grew out of the 'bridge' across the injury site, and into the spinal cord beyond.

"This is one of the best demonstrations of successful growth in chronic injuries we've seen," said Kleitman, program director of repair and plasticity at the National Institutes of Health in Bethesda, Md. "But it's also one of the first of its kind. It will take quite a bit more work to build on this proof-of-principle to figure out how to make such a strategy practical, safe and effective in clinical settings."

Glimmer of Hope for Spinal Cord Patients

The new study could offer a new direction for research on human patients as well. All studies in the past have been targeting treatment right after spinal cord injury, which means that a quarter of a million spinal-cord patients who suffer from chronic injury were being left out. Nerve cells in this study were shown to re-grow a year after the injury.

The implications of the research, experts agreed, are significant.

"ndividuals with long term, chronic injuries, could equally benefit from a treatment [as those with acute injury], when it comes available," says Dr. George Smith of the University of Kentucky.

And the findings also offer a glimmer of hope for researchers in the field.

"t hammers home that given enough research money, resources, and manpower, it can be done, and that spinal cord regeneration research shouldn't be limited to those freshly injured, but that major improvement in those chronically injured is potentially in the (distant) future," Jenkins said.

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