Paralysed Rats Made To Walk Again

We have all heard of mind over matter, but is it possible that the right motivation can actually help repair spinal damage? I have come to Lausanne, Switzerland, to find out about some innovative research being done to repair the spinal cords of rats using pharmaceuticals, electrical signals. And the key ingredient? Motivation. Sometimes, with the right motivation, anything is possible. Tres bien.

The main function of the spinal cord is to transmit neural signals or messages between the brain and the rest of the body. So when the spinal cord is severed or crushed, these messages can’t get past the injury. The result is often chronic paralysis. Research in this area generally focuses on regenerating damaged nerve fibers, but here in Lausanne, they are taking a different approach.

Bonjour, Derek.
Bonjour.
Welcome in the lab.
Ah, thank you.

Professor Courtine’s work with rats is producing remarkable results. >> So I thought, what can we actually deliver to the spinal cord, the kind of information that the brain would deliver naturally in order to walk?

The rats have their spinal cords cut in two places. Although not completely severed, signals can’t get past the lesion, leaving the rats paralyzed. To reactivate the healthy but disconnected neural cells below the injury, the researchers administer a cocktail of synthetic neural transmitters followed by electrical stimulation.

I am cutting the cable that connects to the electrodes on the spinal cord so we can provide the stimulation to the spinal cord.
Ok. So there are cables that run down the spinal cord?
It actually runs under the skin and then it is sutured on top of the spinal cord.

This electro-chemical combination mimics the input of the brain and reawakens the spinal cord below the lesion.

Now I start the 20 immediately. Oh, as soon as that is working. It is amazing, right?

The result? After a few weeks of training and while on the treadmill, the rat is incredibly able to walk again.

So this animal was completely paralyzed five minutes ago and now she is doing {?} stepping on the treadmill. And now we have got 20 speed. Even got the... the animal is capable of {?} on the treadmill. And look at this. You can let him do it yourself. I would stop the treadmill. Oh, she stands immediately.

But this is happening without the involvement of the brain. At this stage, the rat’s stepping is stimulated by the treadmill. The legs are moving independently of the brain, so the movement is completely involuntary.

You can train rats on this treadmill for two months. You will not see recovery of voluntary control. Why? The brain is not involved. There is no motivation to work, because we see that the rat...

Motivation is the key to restoring voluntary movement. So this is when the irresistible Swiss chocolate comes in. I brought a chocolate éclair. I ate half, but the other half is for the rat.

Yes, eat.
She does like it.
She likes it.
We have a combination of like actually yogurt and chocolate which the rat loves.

This reward-based training without a treadmill was the focus of the next phase of research.

I have to get her in the right position.

They designed a special robot which only supports the paralyzed rat, but doesn’t propel it forward.

This means that the rats really need to generate the propulsive forces to go to the reward, which is the chocolate.

So the rat is asked to go and to push herself forward. But she does get a little bit of help up and down.

So the rats have, again, been given electro-chemical stimulants, but without the treadmill, the rat has to decide for itself if it wants to walk.

When you want the animal to participate very actively, I mean, we are talking about the championships of rehabilitation, you know? You need to motivate the rat at any cost.

Come, come, come, come, come.

So Rubia does whatever it takes to coax the rat to walk.

Come on, jump, go forwards. Come on. Push, then push. Push it. Push and come on.
Go, go, go, go, go, go.
Come on. Keep going.

The rat is now walking when it wants to, which means the brain’s signals are getting through to the previously paralyzed limbs.

Wow, she has done really well.
Yeah.

The rat’s spinal cord seems much more capable of rewiring itself than anyone expected. In one of the most extensive examples observed, it has been able to detour around the injury and reconnect the dormant neural network.

What we observe is that the cut fibers, basically, they grow and deliver to this {?} injury enough information. We don’t know what kind, but sufficient information from the brain to have voluntary control.

What we are hearing is evidence of the rat making the decision to walk. The popping sound is a neuron firing. And here she is just standing, but you will see once she starts walking, there is a pretty clear pattern of the activity of the neuron with the rat stepping.

It is showing that the movement is voluntary.
That is really cool. That was really exciting the first time that happened, because, you know, we had this idea that the brain should be involved, but it hadn't been proven.

Go, go, go.

There is a whole team of people working, and everybody is pushing the rat and everybody is all go, go, go. And I could hear it before it happened. And I really knew, ok, it is going to work this time.

Perfect.

Wow. With half of all human spinal injuries leading to chronic paralysis, Professor Courtine’s research gives new hope to those affected.

So, of course, the next obvious and, you know, exciting goal is to try this type of intervention in humans. I don’t know, it is difficult to say what this will achieve in humans. But, you know, it is a very promising new path.