Paralysed rats taught to walk again

An experimental rehabilitation method has enabled paralysed rats to walk again, scientists have today revealed. The remarkable feat has featured heavily in today’s news, which has emphasised both the leap forward it represents and the fact that it is still far too early to consider it as a treatment for humans.

During the study, rats had two partial cuts made in their spinal cords. These cut all direct signals for controlling their hind legs, but left gaps where nerves might potentially form new connections. Researchers then gave the rats a course of drugs injected into the spine, electrical nerve stimulation and physical training designed to make their bodies generate new nerve connections and bypass the site of the cuts. During the training rats were placed in a robotic harness that fully supported each rat in a standing position, but allowed them to walk if they were able to move their legs. The rats were encouraged to walk around by placing treats in front of them. Over time, intensive training allowed some to walk forwards and, eventually, to walk, run, climb stairs and pass objects while being supported by their harness.

There is a risk that this research could be seen as a ‘cure’ for human spinal cord injuries. Although this seems to be a major step forward in scientific terms, it is still far too early to say what impact (if any) this will have on human treatment. The follow-up studies to this eye-opening research will surely be followed with interest.

Where did the story come from?

The study was carried out by researchers from the University of Zurich and other institutions in Switzerland. It was funded by the European Research Council, an International Paraplegic Foundation Fellowship, the Neuroscience Center Zurich, the European Commission's Seventh Framework research programme, and the Swiss National Science Foundation.

The study was published in the peer-reviewed scientific journal Science.

The media presents the research well and makes it clear that this study was performed in rats, rather than in humans. Most newspapers also publish pictures of the rats in their robot-assisted harnesses attempting to walk up stairs, which is a unique and eye-catching image that makes it clear how the rehabilitation process was performed.

What kind of research was this?

This research aimed to investigate whether rats with a spinal cord injury could have some level of hind-leg movement restored using a combination of electrical nerve stimulation, drugs and a movable robotic device designed to support them in an upright position. The research involved 27 rats with lower-limb paralysis as a result of partial severance of their spinal cord, which left them unable to walk using their hind legs.

Animal research can be an important first step in furthering our understanding of disease processes and investigating new treatments. However, this research is at a very preliminary stage and has little immediate application to human paralysis. Also, apart from the obvious differences between rats and humans, the type of artificial spinal injury induced in the rats cannot be considered directly comparable to the different types of spinal damage or injury that can result in human paralysis.

What did the research involve?

In this research rats had two half-cuts made into their spinal cord at slightly different levels – one cutting through the left side of the spinal cord, and another slightly lower down passing through the right side of the spinal cord. The spinal cord was not completely severed, but together the cuts interrupted all direct nerve pathways passing along the spinal cord from the brain. As a result of the two cuts in the spinal cord, the rats were left with complete loss of movement in their hind legs.

To reactivate the nerve pathways below the level of the spinal cord injury the researchers applied electrical stimulation over the rats’ lower backs, and administered a cocktail of nerve stimulant drugs. This stimulation theoretically enables sensory fibres below the level of the spinal injury to provide some source of control for movement.

The researchers demonstrated that, after being treated with electrical stimulation, rats placed on a treadmill began to make stepping movements as a result of the stimulus of the moving treadmill belt. This wasn’t their own voluntary movement of their hind legs, but instead was judged to be due to the sensation of the moving floor. The researchers demonstrated that signals from the rats’ brains were not stimulating this movement, because when they placed them in the harness of the robotic device they were not able to make their legs move. The harness device fully supported the rat in an upright position but otherwise provided no stimulant for movement. As expected, without the sensory stimulus of the moving floor the rats were unable to move their hind legs and remained paralysed.

The next stage of their research was to see whether continued training using both electrical and chemical nerve stimulation and the robotic device could eventually enable the rats to make voluntary movements with their hind legs. They did this first by continuing the electrical and chemical nerve stimulation combined with treadmill-based training. They then aimed to try to promote the development of new nerve connections around the level of the spinal cord injury, which would theoretically allow the brain to regain some control of their muscles. They tested this theory by continuing to place the rat in the harness of the robotic device but on a static floor, rather than the treadmill, and encouraging the rat to move forwards to reach treats.

What were the basic results?

The researchers found that the first difficult voluntary steps were made after the first two to three weeks of continued training. Very basically, the researchers demonstrated that over five to six weeks some rats were then able to make sustained movements, eventually climbing stairs and moving over obstacles with the aid of the supporting harness. The fact that the rats were able to regain some locomotion was taken to demonstrate that electrical signals coming from the brain were able to reach the leg muscles, bypassing the level of the injury via new nerve connections.

How did the researchers interpret the results?

The researchers concluded that by using training to encourage paralysed rats to make voluntary movements they had triggered the recovery of nerve connections around the partially severed spinal cord. This once more allowed motor nerve signals to pass from the brain to below the level of the spinal cord injury.

Conclusion

Spinal cord injuries are a major cause of paralysis and disability, often occurring due to traffic accidents and combat injuries. There has been a great deal of research looking at various potential treatments, ranging from physical therapies to stem cells, although, to date, none has resulted in a viable clinical treatment.

This latest research demonstrated how a combination of electrical stimulation, chemical nerve stimulants and physical retraining helped improve the movement of rats left partially paralysed as a result of cuts made to their spinal cord. This course of therapy involved administering a combination of electrical stimulation and chemical stimulants to a rat with a partially severed spinal cord, and then supporting them in a harness in a movable robotic device. This was done until the rat was gradually able to regain movement in its previously paralysed hind legs and walk again. It appears that the nerve stimulants combined with stimulus training had enabled the rats to form new motor nerve connections (signalling to muscles) around the site of their injury.

Although perhaps it constitutes a scientific breakthrough, this study represents very early stage research and it’s difficult to see what direct impact this animal research will have on human spinal cord injury patients of today. This is particularly the case given the artificial nature of the injury. The researchers had made two half-cuts in the spinal cord at slightly different levels – one cutting through the left side of the spinal cord, and another slightly lower down passing through the right side of the spinal cord. This interrupted all direct nerve pathways passing along the spinal cord from the brain, but did leave an interweaving gap of intact tissue, thereby potentially allowing some maintenance or development of nerve connections across the level of the injury.

Lower-limb paralysis in humans may be caused by many different types of damage or injury to the spinal cord. Although this research did intend to mimic spinal cord injury in humans it is unclear how comparable they are and whether humans with spinal cord injuries would be able to make new nerve connections around the level of an injury as a result of electrical and chemical stimulation combined with movement training.

Also, the rats did not make a full recovery, instead regaining the ability to make movements when supported by a harness, so notions that the therapy could one day be a ‘cure’ for paralysis should be regarded with caution.

There is a continuing need for research developments to try to find new treatments that could help humans with paralysis after spinal cord injury to regain movement. This study is a promising step in the right direction, but a possible new human treatment as a result of this animal research is a long way off.