Spinal cord injury in mice

New hope has been given to people suffering from spinal cord damage after an animal experiment found that mice were able to regain the ability to control their legs after partial spinal cord injuries, reported the Daily Mail . The “animals are able to adjust to their injury by diverting messages from the brain, around the damaged area, to the limbs”, the newspaper explained.

The newspaper story is based on a laboratory study in mice that sheds light on the mechanisms behind spontaneous recovery from spinal cord injury and will be of interest to scientists. The more that these mechanisms are understood; the more likely it will be that effective treatments can be developed. Although some people do spontaneously regain some function following spinal cord injury, the prognosis and degree of residual disability following damage to the spinal cord in any given individual, is dependent on many different factors and can vary immensely. Obviously, mice are not structurally identical to humans and any treatments based on these discoveries are a long way off.

Where did the story come from?

Dr Gregoire Courtine and colleagues at the University of California carried out this research. The study was funded by grants from the National Institutes of Health, the Christopher and Dana Reeve Foundation, the Adelson Medical Foundation and the Roman Reed Spinal Cord Injury Research Fund of California. It was published in the (peer-reviewed) medical journal: Nature Medicine .

What kind of scientific study was this?

This was a laboratory study conducted in mice. Initially, adult mice received an injury at to the nerves at the level of the 12th thoracic vertebrae on one side of their spinal cord. The researchers looked to see how this affected the function of the hind limb (on the same side as the injury) and they also examined the lesions along the spinal cord that developed after the injury. The researchers monitored the function of the hind limb over time – by watching how the mice moved on a treadmill and by taking 3-D videos to look more closely at the movements and joint angles – to see whether the mice recovered any of their function.

The researchers were interested in how the mice recovered some of their function. They were particularly interested in whether the nerve connections were re-established between the brain and the limbs or whether the nerve signals were finding another way to bypass the lesions on the spinal cord and restore movement to the hindlegs. To investigate this, the researchers used a chemical dye to trace the nerves from the limbs back to the site of injury. The dye shows the path of the nerves and indicates whether whole nerves were being regenerated from the brain. The researchers investigated what happened when they gave the mice injuries at different points along the spinal cord – on the opposite side to the original injury. These investigations allowed them to further explore the site and mechanism of recovery.

What were the results of the study?

The researchers found that the mice that had an injury to one side of their spinal cord were unable to use the hind limb on the side of the injury. However, the mice recovered a lot of their stepping ability and other movement between two and seven weeks after the injury. The researchers discovered that recovery of the function was due to the nerve information bypassing the lesion on the spinal cord on the opposite side to the injury. This was confirmed when mice who recovered from the first injury were also given an injury to the opposite side and they then remained paralysed with no improvement in function.

Using a nerve dye, the researchers showed that the recovery of function was not because the long nerves were regrowing from the brain, but rather that there was a localised improvement in function. The researchers also established that when they cut all the nerves from the brain to the lower limbs on both sides (by first injuring one side at one site on the spine and then 10 weeks later another site on the other side, higher up), the mice were able to recover their function by reorganising nerve connections both inside the spinal cord and also around the sites of the injury.

What interpretations did the researchers draw from these results?

The researchers conclude that their findings have important implications for the development of strategies to improve function after spinal cord injury. They say that meaningful functional recovery can be regained by remodelling local nerve connections and it need not focus entirely on re-establishing nerve connections between the brain and the centres that control limb movement.

What does the NHS Knowledge Service make of this study?

This laboratory study in mice uses recognised scientific methods to explore an important area – spinal cord injury. However, experimentally induced spinal cord damage in mice is very different from the wide range of spinal injuries that may occur in humans.

• The findings will be of particular interest to the scientific community who are interested in the mechanisms that underlie injury to the spinal cord and how in some cases function can spontaneously recover to some degree. 
• The more that scientists understand how such healing occurs, the more likely that there will, in time, be some application of the findings to treatment for humans who are suffering the effects of spinal injury. This study was not assessing the effects of any interventions and such treatments are a long way off.

Sir Muir Gray adds...

This is important information showing that the powers of recovery are greater than thought.