AREAS OF RESEARCH

Axon Guidance, Synapse Formation and Neurotransmission
Spinal cord researchers have had increasing success coaxing nerve cells, or neurons, to regenerate their damaged axons following a spinal cord injury. However, to rebuild nerve circuitry and restore lost function, those new axons must travel distances up to several feet, recognize their target neurons, and forge working connections, or synapses, with them. Neurotransmitters, chemicals that facilitate neuron-to-neuron communication, must also be replaced. So too must a host of receptors, the molecular sentinels that intercept the external signals that control the behavior of a neuron. A growing number of researchers are studying developing organisms to see how their brains and spinal cords assemble their complex wiring in the first place. If this process could be restarted in the adult, then doctors would have a valuable tool for repairing the injured spinal cord.

Cellular Replacement, Stem Cells and Artificial Substrate
One approach to spinal cord repair involves replacing the neurons and the cells that support them, which are destroyed or damaged by an injury and its aftermath. Toward that end, some scientists are trying to generate dependable lines of primitive spinal cells that, when transplanted, would evolve into the cell types needed to fix the injured cord. Others are investigating transplant techniques, including one that includes transplanting both cells and tiny bridges or tunnels that direct and support replacement axons as they grow across a breach in the spinal cord. Still other researchers hope to restart the mechanisms that first created the nervous system.

Concomitant Function
In addition to paralysis, spinal cord injuries cause a range of complications, some life threatening. The problems include infection, pneumonia, spasticity, chronic pain, and blood pressure and temperature irregularities. Scientists are increasingly turning their attention to these difficult-to-treat conditions that affect both the health and the quality of life of the spinal cord injured.

Growth Inhibition
Unlike cells in the peripheral nervous system, cells in the central nervous system do not regrow after an injury. Spinal neurons might replace their damaged axons, however, were it not for the body's complicated responses to a trauma. These complex responses transform the area around the lesion into hostile territory for axon regeneration. Scientists have identified a number of so-called growth inhibitors. If treatments could be developed to stymie these inhibitors or prevent them from congregating at the spinal lesion, then the body might repair lost nerve circuitry.

Neuroprotection
For weeks and possibly months after a spinal cord injury the cellular casualty count rises. The body's immune response and toxic chemicals released by dying cells attack cells that survived the initial injury. Other cells just seem to know that something in their neighborhood is terribly wrong, and they self-destruct, a process called apoptosis. This mayhem amplifies the lesion and the loss of function. If this biological ripple effect could be prevented the injury might wreak less havoc.

Promotion of Axon Growth and Remyelination
Although spinal cord injuries destroy axons, the cell bodies to which they belonged often survive. But unlike nerve cells in the peripheral nervous system, neurons in the spinal cord and brain cannot repair their damaged axons or grow new ones. One approach, then, to treating spinal cord injuries is to reprogram neurons so that they can spout new axons that would recreate the nerve circuits an injury destroys. However, for new axons to work properly they need to be enwrapped in myelin, a fatty substance that insulates and protects them. A spinal cord injury also can cause demyelination, in which axons that survive the initial trauma then lose their myelin in a process similar to what occurs in multiple sclerosis. Researchers are pursuing strategies to trigger axon regeneration or myelination following an injury.

Rehabilitation
Rehabilitation therapy helps to maintain bone and muscle mass and is vital for maintaining the general health of people with spinal cord injuries. Yet evidence is mounting that certain forms of rehabilitation also may lead to beneficial changes in the spinal cord itself. For example, nerve circuits above and below an injury retain their ability to reshape themselves to become more efficient and even to assume new roles, a quality known as plasticity. Some of these adaptations can be initiated or enhanced by vigorous exercise. For example, a training routine that involves assisted stepping on a moving treadmill spurs plasticity and improves walking and standing in animals and people with certain types of spinal cord injuries. Known as locomotor training, this approach also may improve function by promoting axon regeneration and improving communication between nerve cells.