How a goldfish keeps its nerve
Research into how animals repair damaged tissue may help spinal injury victims, says Paul Rodgers
Monday 30 September 1996
It is our ability to even ask such questions that is at the heart of the problem. According to Professor Michal Schwartz at the Weizmann Institute of Science in Israel, mammalian nerve cells have traded a talent for regeneration for the ability to learn. In general, the bargain benefits humans; except when injury to the spinal cord - the 45cm, finger-thick bundle of nerves running through 38 vertebrae - leaves us without feeling or the use of our limbs.
Schwartz's theory is based on the earlier discovery that the action of the immune system is suppressed in the brain. She says this is partly because the process of learning involves rewiring the billions of connections between neurons. An automatic repair mechanism that returned this network of nerve cells to its original form would cause something akin to amnesia. "Clearly you don't want interference from outside systems," she said.
This may explain the goldfish's famous short memory - said to last only as long as it takes to swim around a bowl. Its immune system may be wiping its memory as it swims.
But this leads to the idea that the same suppression of the immune system in higher organisms also stops regrowth of the neurons, which occur in the brain, spinal column and optic nerve. Experiments by Schwartz and her team offer evidence that this is the case, and also suggest a way of getting around the problem.
One of the curiosities of spinal injuries is that the damage done to the nerves tends to be greater than would be expected from the initial injury itself. With ordinary organs, such as the skin, the first reaction to damage is the release of chemical messengers which attract macrophages, cells in the immune system that gobble up foreign bodies and the remains of dead cells, to the site of the wound. These release hormones which promote regrowth of the damaged cells. The arrival of the macrophages is visible even to the non-scientific eye, being signalled by swelling.
But when spinal nerves are damaged, the swelling is much less than in other parts of the body. Schwartz found that the nerve cells were giving off a chemical - she dubbed it Immune Privilege Factor - that discouraged macrophages from coming to the site of the injury, and stopped them from doing their work if they did show up.
Without the macrophages to effect a cleaning operation, toxins released from dead cells went on to damage neighbouring healthy ones. The suppressed macrophages also appeared to release highly reactive free radicals, which added to the damage. Without the hormonal doses, the remaining nerve cells made no effort to rebuild connections across the damaged section.
The odd thing is that this does not apply to parts of the nerve cells that extend to the rest of the body. The long tendrils known as axons that connect one nerve cell to another can stretch the length of the spinal column, or to the extremities of the body. If a cut on your finger severs an axon, the immune system reacts normally and the damage is repaired.
In Schwartz's experiments, the neurons of a rat's optical nerve were severed. She took blood samples from the animal, separated the macrophages, and in a test tube exposed a damaged axon from elsewhere in the rat's body to them. The macrophages became activated; when they were then injected into the damaged optic nerve, they began removing the debris of the dead cells and releasing their healing hormones.
Schwartz is cautious about predicting a cure for paralysis, though she does think doctors will eventually use a technique similar to her own. It is theoretically possible to come up with a drug that blocks Immune Privilege Factor. The problem would be to keep it from spreading to other parts of the central nervous system, where it could play havoc with memory and learned responses. Injected macrophages might also spread to some extent, though probably not as far.
Other researchers favour a drug-based approach. Schwartz says her work is based in part on earlier studies by Professor Schwab at the Swiss Institute for Brain Research. He has not only identified two growth inhibitors, but also developed antibodies to block them. Treated with these, axons that would normally sprout for a millimetre and then halt will keep growing for a centimetre.
An effective clinical treatment, however, is years away. Schwartz measured her success by counting the new fibres that had grown across the surgical cut made in her rat's optical nerves. It did not measure how well the new connections were working - something the team is now trying to discover.
Another question is whether the treatment works only when a wound is fresh. If so, it would be of little help to Mr Reeve and others who have been injured in the past. But it could provide a new life for future victims of spinal injury.
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