Stroke and spinal injury

This essay was written by Geoff Raisman and was first published in the 1995 Mill Hill Essays.

When a farmer, or a machine operator has a finger cut off, surgeons can sew it back on again. But when Christopher Reeve, the actor who played “Superman”, had a riding accident and severed his spinal cord, he was confined for life to a wheel chair. Why can’t we simply sew his spinal cord back together again? When the boxer Michael Watson had his brain damaged by a blood clot, it did not get better. What has happened, and why are we not able to repair the damage?

The brain and spinal cord are two of the most precious parts of our bodies. They are made up of the most delicate substance – nervous tissue. To protect it from injury, the brain is surrounded by the hard bone of the skull. The spinal cord is similarly encased in a series of strong, rigid vertebrae fitted end to end, making up the flexible backbone. These delicate nervous tissues are the place where all our memories and experiences are stored. They are the source of our feelings when we are awake, and our dreams when we are asleep. Without them we would be unable to see, smell, hear, touch, or taste, unable to move or to respond in any way to the world outside.

Fortunately, the strong, protective bony coverings usually protect the brain and spinal cord from any injury, even though we put our bodies through violent movements, fall, bend and twist our backs, and use our heads to head footballs. But, in some cases, these defences are exposed to violence too great for them to withstand. The neck is the most vulnerable part of the body. When it breaks, the bones of the backbone snap, and crush the delicate spinal cord. The effects are instant and catastrophic. The injured person loses sensation in the body, and is unable to move. In many cases, these effects are permanent. The disability is a life-long sentence.

Another form of injury can occur when there is no violence. Deep inside the skull, small blood vessels break, and bleed. The nearby parts of the brain lose their blood supply, and within minutes, they die. This is called a ‘stroke’. It too leads to paralysis on the affected side of the body, and loss of the ability to speak. The patient may recover slowly, to a varying degree.

What is the reason for these symptoms, which are so devastating to the life of the sufferer, and to the family and friends? And are there any prospects that we may one day develop treatments for disabilities which are, at the moment, incurable? To the naked eye, the brain and spinal cord seem to be made of a semi-solid substance, with no obvious internal organisation. But at very high levels of magnification it can be seen that they are made up of many millions of tiny nerves, like wires of great length, passing from the brain down to the body, and from the body back up to the brain. Like the wires of an immense telephone exchange, these nerves carry information at high speed from one part of the body to another. But we should remember that the nervous system of every single individual man or woman is infinitely bigger and more complex than the entire combined telephone networks of every country in the world.

What has happened in the patients with stroke or spinal injury is that nerve connections have been broken. The effect of a stroke is to destroy the connections that carry messages from the brain to tell the body what movements to make. The injured person is perfectly able to decide what he or she wants to do, but the body refuses to obey. The limbs do not move as they used to do before the injury. The patient is unable to speak the words that come to his or her mind. The effect of a spinal cord injury can be even more devastating. The spinal cord is like a narrow, highly congested motorway. In addition to the nerves whose messages tell the body what movements to make, the spinal cord also contains the nerves carrying messages in the opposite direction – from the body to the brain. These messages tell the brain where the parts of the body are, and what is happening to them. When the spinal cord is damaged, the patient is not only unable to move, but also unable to feel. He or she is in danger of being cut by sharp edges or burned by hot objects that the rest of us are readily able to detect and avoid.

So what might be done to repair the nervous pathways disrupted by such injuries? Nerve fibres are not arranged at random. Each nerve consists of a fibre, which is attached to a nerve cell. Messages start in the nerve cell, and are carried down the nerve fibre. When they reach the end of the nerve fibre they are transmitted to the next nerve cell. So the passage of messages through the nervous system is like a series of relay runners passing a baton on from one runner to the next. When a nerve is damaged, the part of the fibre which is separated from the cell body breaks down and dies. Although the nerve cell body still survives, it has lost the pathway which it needs to send information to the next cell. The ability to relay messages is lost.

If it would be possible to make nerves regrow, then they might be able to grow back to their original destinations, remake their contacts, and re-establish the original relays of messages. Movement and sensation would be restored to patients with brain and spinal cord injury.

There is now some evidence that it might be possible for damaged nerves to regrow given the right circumstances. When a nerve is damaged, the part of the fibre which remains attached to the nerve cell does not die. Instead, like a tree which has been pruned, the cut end sends out sprouts. These sprouts are not able to regrow for any useful distance, but their presence is a reminder that inside the brains and spinal cords of injured people, the nerve cells seem to be making an effort to regrow. The problem then becomes, what can be done to help these sprouting nerve fibres, and make them able to reconnect to their original targets?

Every part of the body is supplied with nerves. The nerves of the arms and legs connect to the nerves in the brain and spinal cord. The nerves of the arms and legs are the routes which carry commands from the brain and spinal cord to the muscles, and carry sensations back to the brain and spinal cord from the skin. When a nerve is injured in an arm or a leg, the effects are different from those when the same nervous pathway is damaged in the brain or spinal cord. A common arm nerve injury, for example, is damage to the nerves in the wrist. These nerves can be severed when there is a cut across the front of the wrist. The effect is that movement and sensation is lost in the hand. But, unlike the permanent effects of brain or spinal cord injury, injuries to nerves in the wrist can be repaired. The cut nerve fibres not only sprout, but these sprouts are able to grow back along their original pathways into the hand, and restore it to its normal working.

What is it then that makes nerves outside the brain or spinal cord able to grow back to their original positions? The nerves of the arm or leg do not travel alone. They are accompanied by special cells, called sheathing cells. The sheathing cells form a kind of insulation, wrapped around the nerve fibres. When a nerve regrows in the arm or the leg, the first thing that happens is that the sheathing cells grow out of the cut end and make a living pathway. The sprouting nerve fibres grow on to this pathway. The sheathing cells are able to maintain the growth of the sprouting nerve fibres, carry them across the injury, and lead them back to their original destinations. Recent experiments have shown that if sheathing cells from arm or leg nerves are transferred into the brain or spinal cord, they can also make cut nerves regrow in the brain and spinal cord. Therefore the use of sheathing cells may be an important step in trying to repair brain and spinal cord injury.

Sheathing cells have two ways of acting on cut nerves – first they provide the tracks along which the nerve sprouts grow, and second, they produce growth substances that stimulate the growth of nerves. One of the ways in which sheathing cells might be made more effective is by inducing them to produce more growth substances. So far a small number of growth substances have been identified, and are available for use. We can use sheathing cells as a method of applying these growth substances to injured nerves in the damaged brain and spinal cord. In the first step, living sheathing cells are grown in a dish. Then the genes needed to produce the growth substances are added to the sheathing cells. The living cells take up these genes, and as a result they become able to make the growth substances themselves. When these ‘improved’ sheathing cells are placed at the site of a brain or spinal cord injury, the extra power supplied by the additional growth substances further promotes the regrowth of the damaged nerve fibres.

This research suggests that the tragic effects of stroke and spinal injury may not always need to be permanent in the future. Damaged nerves in the brain and spinal cord show sprouting responses which, if encouraged, could lead to true repair of the injury. We still do not know all the steps needed to make nerves regrow successfully all the way to their original destinations. But by working with the body’s own cells, such as sheathing cells, and natural growth substances, we can take advantage of the growth powers present in the patient’s own brain and spinal cord.

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