Alberta Innovates- Health Solutions

What we sense, what we think, and how we respond to the outside world is controlled by an intercellular communications network called the nervous system. The central nervous system (CNS) is composed of nerves (neurons) in the brain and spinal cord and functions as the master switchboard in the body.

But the CNS is just one of two systems of nerves in mammals. The peripheral nervous system (PNS) (peripheral meaning lying outside the brain and spinal cord) is as elaborate and complex as the CNS, consisting of sensory (sensation) and motor (movement) nerves. All PNS neurons have the same basic parts-

• a cell body that receives and gives instructions,
• a tube-like unit called an axon that connects the cell body to either sense organs or muscles.

Sensory nerve cell axons carry messages from sense organs to the CNS which results in movement via activation of the motor nerve cells.

Scientists have always known PNS nerves could repair and regenerate.

"When peripheral nerve cells are severely damaged, axons which are cut off from their cell bodies die and must be replaced by axonal regeneration from the damage site. Muscles are paralyzed and sensation is lost, at least until the axons grow and remake functional connections with muscles and sense organs," says Heritage Scientist Dr. Tessa Gordon, who is studying peripheral nerves at the University of Alberta. "Although we know axons can regenerate, in reality the amount of function recovered is disappointing. Axonal regeneration has been observed to occur at a rate of 1 to 3 millimetres per day in the body. The onset of regeneration, however, may be very slow; regenerating nerves must cover huge distances, and often simply fail."

The distance between the site of injury and the part of the body it affects can be more than a metre long. By the time the axon could repair and grow new connections, more than a year would have passed. Before that, irreparable damage would have occurred without the vital signals and information from the nerve.

Dr. Gordon's research tackles this issue of why, with the capacity for regeneration, does repair fail to happen. By using motor nerves, which have an enormously amplified effect on muscle cells (about 300 to 1000 muscle fibres are activated by one motor nerve), she measures the effects of injury on specific areas of tissue.

With the injury of a nerve cell's axon, many changes occur in the cell body. It switches from a mainly signalling role to one of promoting nerve cell growth. Schwann cells turn up gene regulation in order to express certain nerve growth factors that guide the now-growing axon back to its target. After a short period of time, though, this gene expression falls back.

Dr. Gordon studies a number of chemical factors involved in injury repair in an effort to decipher their communications. She suspects that after nerve cell injury, the immune response mounted by the body (cytokine production) produces a favourable but temporary growth environment. She also manipulates certain intracellular nerve growth factors to prolong the optimal window of time needed for nerve repair. But her most surprising results have been from using electrical stimulation.

"We cut a nerve that contained both motor and sensory axons. At two weeks, regeneration was occurring but many of the wrong nerves were growing to each target, which delayed overall growth. At four, six and ten weeks, more and more of the right nerves were growing to their targets, but the number in the wrong branch stayed the same. When we repeated the same experiment with low-frequency electrical stimulation, we found a dramatic acceleration not only of overall growth, but specifically, of growth of the right nerves to their targets," says Dr. Gordon.

Admittedly, there are risks involved in manipulating nerve regeneration. "For example, some nerve growth factors produce hypersensitivity and pain." Nonetheless, Dr. Gordon looks forward to the time when her work, and that of many other neuroscientists, could lead to real applications for people with peripheral nerve injury.

Dr. Tessa Gordon is a Heritage Medical Scientist at the University of Alberta. She also receives funding from the Medical Research Council of Canada, the Canadian Neurotrauma Research Program, and the Paralyzed Veterans of America Spinal Cord Research Foundation.