Scientists find a way to regenerate damaged peripheral nerve cells

An old trick to the rescue of a problem? Yes, that was what has happened when doctors used a similar technique in a study of patients with chronic, incomplete spinal cord injury — patients whose spinal cords are injured but in such a way that some communication between the brain and spinal cord exists, allowing limited feeling and movement. In that study, doctors encouraged recovery of movement by alternating between a 9 percent oxygen environment for 90 seconds and a typical 21 percent oxygen level for 60 seconds, for 15 cycles. The idea was to “stress” the neurons spared by injury and see if that improved their function.

Now another set of researchers used the same technique to regenerate damaged neurons or nerve cells and the low oxygen environment that may stimulate the damaged neurons to start regenerating and improve recovery.

One of the big challenges with spinal cord injuries is that spinal cord neurons don’t have the ability to regrow after an injury. That’s why most spinal paralysis in patients is permanent. So scientists tend to focus their research on regrowing peripheral neurons – those that extend from the spinal column to the tips of the hands and feet. Peripheral neurons in the body’s extremities have the ability to regenerate, helping people regain some movement and sensation.

In new research, scientists at Washington University School of Medicine in St. Louis have identified a master gene involved in orchestrating the regrowth of peripheral nerves. The gene works as a main switch, making other genes “flip on” in a domino-like fashion. Understanding how these nerves regenerate one day may aid efforts to regrow spinal cord neurons, the researchers said.

The findings are published online Oct. 29 in the journal Neuron.

Senior author Valeria Cavalli, PhD, associate professor of neurobiology, has shown that injury to peripheral nerves flips on a master gene, called hypoxia-inducible factor 1-alpha, otherwise known as HIF-1alpha. This gene, in turn, activates some 200 genes involved in the regrowth of peripheral nerves.​​​​​​​​​​​​​​ What is interesting about HIF-1alpha is that it is known to be sensitive to how much oxygen is in the cell. If the oxygen level is normal, there isn’t much H1F-1alpha, but in stress conditions such as a lack of oxygen, there is more of this gene to protect the cell and organism from this stress. This knowledge gave the researchers the opportunity to use a noninvasive tool to increase the levels of this factor by simply decreasing the levels of oxygen.”

In the lab, Cavalli cultured neurons in a plastic dish and used a zero oxygen environment to measure the regrowth of nerve axons, the branches of nerve cells that transmit nerve signals. In other experiments, the researchers stressed out mice, putting them in 8 percent oxygen environments for 10 minutes, followed by normal air – about 21 percent oxygen – for 10 minutes. They repeated this cycle six times.

What they found was that the “stressed out” neurons responded by growing the nerve axons that connect to the muscle (motor neurons) as well as those that connect to the skin (sensory neurons) much better than those that were not “stressed out” with low oxygen.

Cava​lli only has seen the nerve axon growth under the microscope. She hopes to keep working to find the right balance and answer the questions: Is less oxygen truly beneficial? What about the time limits? Does functional recovery occur faster and better in mice?
Watch this space for answers to these questions.

Source: http://www.cell.com/neuron/abstract/S0896-6273%2815%2900839-9