Signal found? New techniques improve recovery after nerve damage

The peripheral nervous system plays an integral role in the how one’s body functions. With afferent nerves carrying sensory information to the brain and efferent nerves sending signals from the brain to the muscles, nerves are integral in sensing surroundings, communicating information between the body and brain and voluntary movement. Damage to nerves can result in pain, numbness, weakness or paralysis, severely altering quality of life. Luckily, nerve regeneration research is offering promising treatments.

In cases where the nerve has not been completely severed, physiological mechanisms of neuroregeneration can be applied to aid in recovery. Normal nerve cells are coated by myelin, which increases the speed of neuronal transmissions. After neuronal injury, demyelination can occur, impairing the neurochemical signal. Currently, the main route of treatment for demyelination focuses on anti-inflammatory drugs, but research into the signaling pathway for myelination offers new treatment routes. While the process of peripheral myelination is complex, researchers have found the Wnt signaling pathway plays an important role. Lithium chloride, which is used as a mood stabilizer in bipolar disorder, can mimic this pathway. Charbel Massaad at Paris Descartes University has showed that lithium chloride helped thicken myelin sheaths and improve whisker function after sciatic nerve injury in mice.

For injuries in which the nerve is severed, surgical intervention is often required. While successful surgical intervention has improved, full recovery is not always achieved, especially in older patients. Recently, two studies in surgical procedure have shown promise in animal models.

A major limitation to current surgical techniques is the body’s own repair mechanism. George Bittner’s team at the University of Texas Austin has shown that delaying the body’s repair mechanism improves nerve repair. When a nerve is severed, the body’s repair mechanism works to seal the two stumps, but this hinders doctors ability to reconnect them. The sealing of the stumps occurs through the formation of vesicles driven by calcium and oxidation. Flushing of the injury site with a calcium free salty solution containing methylene blue blocks oxidation. Then, the nerve is glued together using polyethylene glycol. At this point the body’s repair mechanism is restarted through injection of a calcium rich salty solution, which forms vesicles that consolidate the join.

Another approach to surgical repair focuses on the development of appropriate scaffolding to help guide regrowing axons. (Axons are the long portions of a nerve cell that conduct signals away from the cell.) Most commonly, doctors use a synthetic material seeded with cells as a scaffold for the growing nerves. A major limitation to this approach has been immune response to the materials. To prevent the immune system from rejecting the synthetic materials or cells, patients are treated with immune suppressive therapies. Jason Huang at University of Rochester decided to investigate new cell types for use in axon regeneration. Traditionally, Schwann cells (cells that form myelin) have been applied to improve axon regeneration. While Schwann cells do improve regeneration, they have high levels of  major histocampatble complex (MHC), which induces an immune response. The researchers realized that neurons such as dorsal root ganglion cells could be particularly useful as they have a reduced expression of MHC. When used in conjunction with a synthetic tube, dorsal root ganglion cells had similar success at axon regeneration as Schwann cells, but without the immune response. This could result in improved tolerance and survival of the scaffold.

Peripheral nerve injuries are a major source of disability. While treatments have greatly improved, full functional recovery is still not guaranteed. As research into this field expands, promising techniques continue to emerge. While the techniques discussed show promising results in rodent laboratory studies, it is important to note that human injuries are much more complex than lab micro lesions; thus, only clinical trials will show the full ability of these techniques.