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20 September 2009

Drug-electricity combo makes paralysed rats sprint

Video: Paralysed rat

Rats with severed spinal cords and no feeling in their hind limbs can walk, run, step sideways and jog backwards without re-growing the nerves between the injured site and the brain, raising the prospect of a treatment for people with spinal injuries.

Although these rats have no voluntary control over their hind limbs, they were able to sprint in a way that was indistinguishable from an uninjured rat after a combination of drugs and electrical impulses were applied to their skin.


Regain movement

“It was incredible to look at,” says neurobiologist, Grégoire Courtine, from the University of Zurich, Switzerland, who led the team doing the experiments.

If it turns out that we possess the same independent networks of neurons as rats, a similar combination of treatments might one day help people with spinal cord injures to regain movement.

The spinal cord is the conduit through which signals of intent to move from the brain are turned into signals that propel muscles into motion. When it is damaged, these signals can no longer get from the brain to the muscles.

Serotonin mimics

Networks of neurons – known as central pattern generators (CPGs) – exist in the spinal cord of rats and mice that can trigger movement without the help of the brain, if stimulated either electrically or with chemicals that mimic various neurotransmitters.

In past experiments, administering these treatments separately has successfully induced rhythmic hindleg movements, but the animals couldn’t support their body weight at the same time.

To see if a combination of the two treatments might do the trick, Courtine and his colleagues first injected rats with severed spinal cords with drugs, including one that mimics the effect of the neurotransmitter serotonin, which is found in the central nervous system and is known to control muscle contractions.

Then they applied steady bursts of electricity to their spinal cords, via electrodes placed on the surface of the skin.

Support body weight

This enabled the animals to walk again, and crucially, after two months’ training, bear their own body weight.

It’s not clear exactly why the two treatments work so well in tandem, but the researchers suggest that the drugs somehow prime the CPGs for electrical activation. “Combining the two created an exquisite synergy: the pharmacological treatment prepares the circuits and the electrical stimulation activates them,” says Courtine.

Crucially, the trained rats could respond swiftly, within a second, to changes in pace and direction of the treadmill. “What is really important is that the spinal circuit is smart,” says Courtine, “We can change the direction or speed of the treadmill and the circuit has the capacity to reinterpret that information and modify the way muscles respond so that the animal can run forwards, backwards or sideways.”

Spinal implant

Courtine’s team are beginning research on a device for people with spinal cord damage, which would be implanted into the spine, below the injury, and wirelessly activated to trigger electrical stimulation. A way of regularly infusing the serotonin mimics near to the target neurons, in order to avoid effects on the rest of the nervous system, would need to be developed too.

One remaining problem is that balance, which is controlled by the brain, does not recover: the rats could only run when assisted by a robotic arm. However, Courtine points out that you could give people a walking frame to help with balance.

Mark Bacon, the head researcher at Spinal Research in Guildford, UK says this is an excellent and important piece of research, but points out that whether it will be applicable to humans is still an open question.

“Although there is evidence that humans may have CPGs, we don’t know if they are capable of acting independently without input from the brain.”

Journal reference: Nature Neuroscience, DOI: 10.1038/nn.2401 (in press)