Rehabilitation and Regeneration- Effectiveness in Treatments of Spinal Cord Injury

According to the National Spinal Cord Injury Association, approximately 250,000 to 400,000 individuals in the United States have spinal cord injuries. Every year, approximately 11,000 people sustain new spinal cord injuries – that’s thirty new injuries every day. The injury comes from damage to the spinal cord that results in a loss of function such as mobility and feeling, and is usually a result of a trauma or disease. (1) One of the most obvious negative effects of a spinal cord injury is the difficulty in walking, forcing many patients to use wheelchairs in order to achieve locomotion. Over the past decade considerable effort has been directed at promoting the recovery of walking and finding effective treatments. The two treatments that are currently considered to be the most effective are rehabilitation and regeneration. Both methods consider a different way the Central Nervous System has of ‘fixing’ itself; regeneration aims to restore a functioning set of connections similar or identical to those present originally, whereas rehabilitation aims for the restoration of function by compensatory mechanisms. In this essay, we will analyze the rehabilitative and regenerative methods of intense training on a treadmill and promoting regeneration of axons in the spinal cord. Which method is more effective in treating spinal cord injuries (SPI)? In order to answer this question it is important to analyze the dynamics of the CNS itself, as well as the concepts or regeneration and rehabilitation and their effectiveness in case studies.

The spinal cord is the major bundle of nerves that carry nerve impulses to and from the brain to the rest of the body. The brain, spinal cord, eye and optic nerve constitute the Central Nervous System. Motor and sensory nerves outside the central nervous system constitute the Peripheral Nervous System. One of the most fascinating things about the difference between these two systems is that the peripheral nervous system (PNS) is able to heal itself after an injury. For example, if you have a bad cut on your toe you may temporarily lose some sensation if a nerve has been damaged. However, the nerve endings in your toe will eventually grow back and re-establish their appropriate connections. When damage is done to the CNS, however, the body is mysteriously unable to restore communication to below the site of neural damage, leading to a more permanent loss of sensation or movement. The approach to "curing" the problem is to concentrate on techniques that hold the promise of repairing specific types of spinal cord damage.

The goal of rehabilitation is to aid people in learning how to care for a body that now obviously works differently. Because of more and more research that is being conducted in this area, mostly with cats and rats, scientists are beginning to see that the idea of rehabilitative training can restore some walking ability to those left paralyzed by SPI. It has been shown that the adult mammalian spinal cord can perform the necessary functions for walking largely independent of the brain. Recent data has also shown that neural circuits governing locomotion in the spinal cord can ‘learn’ to alter their connections and (although it does not necessarily repair itself) find new ways of creating motor function. (2)

Within the past decade there have been a number of major developments in approaches to the rehabilitation of patients with spinal cord injury. One of the most promising is the use of weight-supported training on a treadmill to improve locomotor function in patients with partial spinal cord injury (2). The training consists of partially supporting the patient’s weight and manual assistance of leg movements by therapists. Effective training requires the mimicking of normal movements of the legs, trunk and arms (often by assistance from therapists). This is considered to produce an appropriate pattern of sensory input for driving adaptive changes in neuronal networks in the spinal cord. The introduction of this technique was based firmly on animal research that showed that following the complete transection of the spinal cord in cats, stepping movements in the hind legs could be enhanced by daily training on a treadmill (3). While conducting experiments, the sensory nerve in a calf muscle called the lateral gastrocnemius (LG) was cut. When this nerve is stimulated, the signals it sends to the spinal cord elicit in the leg’s motor neurons responses that prolong stance and calibrate the timing of each step. Within 5 days of having the cats walk on treadmills and stimulation both their LG and MG (medial gastrocnemius, another sensory nerve in the calf muscle), the researchers found that the ability of the severed LG nerves to prolong stance was much lower than that of the controls, while the stance-prolonging ability of the MG nerve in the injured leg had increased. The conclusion that was made from this was that the neuronal circuitry had changed to compensate for an injury-induced deficit (4). The concept behind this research is that inside there is something inside of the spinal cord that innately creates complex movements like walking. Humans have evolved in a way that requires the brain to turn those circuits on, but by retraining the circuits in the spinal cord, it might be possible to enhance motion, even when signals from the brain are blocked.

While it was once thought that CNS cells could not regenerate at all, it has recently been shown that they in fact can, although they do not do so effectively in mammals. Nerve cells in both the central and peripheral nervous systems are associated with helper cells called neuroglial cells. After injury, the CNS helper cells largely inhibit regeneration, while those of the peripheral nerves, the Schwann cells, stimulate regeneration, even in humans. Scientists are attempting to isolate these cells from peripheral nerves and transplant them into the spinal cord to induce regeneration by providing an altered, supportive environment. By introducing these factors into injury sites alone or in combination with grafts, researchers hope to stimulate additional nerve regeneration and promote the health of nerve cells. This approach has been shown to stimulate CNS regeneration, including growth of axons from nerve cells within the spinal cord and those from the brain that send their long axons down the spinal cord. (5) In this strategy, a SCI individual could act as their own donor, since Schwann cells can be obtained from biopsies of peripheral nerves in adults

Although both regeneration and rehabilitation methods are innovative techniques that are attempting to the best of their capacities to treat and eventually repair damage caused by SPI, there are obvious gaps in research and knowledge, as well as questions regarding the effectiveness of both methods. Whereas rehabilitation is thought to be the easiest method for the eventual restoring or motor and sensory function in patients, such treatment does not work in all patients, nor is it one-hundred percent effective.

In contrast to the beneficial effect of treadmill training in patients with incomplete spinal cord injury, similar training in patients with complete spinal cord injury does not lead to sustained stepping movements of the legs, although it does occasionally lead to an ability to elicit swing movements in the absence of any external assistance. No one can know how much improvement individual patients can expect from rehabilitative treatment such as special training. Many patients with spinal cord injuries will most probably not benefit from such an approach, because training is not very likely to produce useful walking in patients whose cords have been so badly damaged that there is no surviving connection between their brains and the region below their injury. These people would have a lot of trouble being able to voluntarily keep control of when their legs started or stopped. Locomotive training does not restore balance. Because of this, quadriplegics like Christopher Reeve would not be able to earn to walk without someone to hold them upright.

In the case of regenerative methods of restoring motor and sensory function, there are obvious scientific roadblocks that have been encountered and lead to the questionability of its effectiveness. Although an enormous amount of research has been done recently and there have been advances in understanding the neurological dynamics of the regeneration of nerve cells in the spinal cord, there is no direct evidence that recovery is due to regenerated axons, although there is a lot of hopefulness for the future. (6)

In conclusion, restoring motor, sensory, and autonomic function to injuries in the Central Nervous System is one of the major issues in the ream of neuroscience. Obviously, the problem of the response of the CNS to injury is extremely complicated and complex. Although there have been several suggested methods to overcome the effects of injuries such as those inflicted to the spinal cord, it is becoming more and evident that there is not one way of approaching the problem. Both regeneration and rehabilitation are problematic and uneven solutions by themselves that have no hope of being entirely successful. The most effective solution seems to be in the blending of rehabilitation and regeneration methods in order to establish a successful therapy that will improve on what we previously thought was no longer attainable. What I find most interesting about the issue of regeneration and rehabilitation is that perhaps they are inextricably linked. Research has shown that functional, regenerative recovery after CNS injury may depend upon the reorganization of undamaged neural pathways, and that spinal cord circuits are in fact capable of this reorganization, in the form of plasticity, which behaviorally manifests itself in the ability to learn new locomotor tasks. (7) Is it therefore possible that locomotor training, in addition to the appropriate stimulation, has the ability to modify and refine synaptic connections? By enhancing locomotor recovery in the form of training after a spinal injury could we in effect spur the regeneration of spinal pathways? Admittedly, much more research is needed in order to fully discover the most effective method of reversing the effects of CNS injuries.

WWW Sources

1) National Spinal Cord Injury Association

2) Locomotor Activity in spinal cord-injured persons

3) Pearson, K. & Fouad, K., Restoring Walking after Spinal Cord Injury, Progress in Neurobiology, June 2004, vol. 73, Issue 2, Pages 107-126

4) Teaching the Spinal Cord to Walk

5) Spinal Cord Injury Treatment and Research

6) Fawcett, J.W. & Geller H.M., Regeneration in the CNS: Optimism mounts, Trends in Neurosciences, May 1998 Vol. 21, Issue 5, Pages 179-180

7) Muir, G.D. & Steeves, J.D., Sensorimotor stimulation to improve locomotor recovery after spinal cord injury, Trends in Neuroscience, February 1997, Vol. 20, Issue 2, Pages 72-77