Nature Podcast：调节脊髓损伤患者血压的神经假体

Host: Shamini Bundell

The first thing that comes to mind when we think about spinal-cord injuries is paralysis, but there are lots of other ways that people can be impacted. One that’s particularly overlooked is blood-pressure instability. Let me give you an example. Imagine you’re lying down, you hear the doorbell ring and suddenly you jump up only to be met by a wave of light-headedness, maybe you even faint. This is caused by your body being a bit slow to react and not increasing your blood pressure fast enough to compensate for your movements. For most people this is an occasional annoyance, but for those with spinal-cord injuries it can be constant and debilitating. That’s because the system responsible for monitoring and maintaining blood pressure – the so-called baroreflex – can be damaged as a result of these injuries. Now, a team led by Grégoire Courtine from the Swiss Federal Institute of Technology have come up with a novel solution – a neuroprosthetic system which aims to monitor and maintain blood pressure for spinal cord injury patients. They’re calling it a synthetic baroreflex. Noah Baker gave Grégoire a call and started by asking him a bit more about the natural baroreflex.

Interviewee: Grégoire Courtine

The natural baroreflex measures the blood pressure. It’s conveyed to specific cells, neurons, that are located in our brain stem, and then when these neurons detect that the blood pressure is too low, they will activate what is called a sympathetic circuit that are located through the spinal cord in order to increase the vital constriction of blood vessels. That’s what increases the blood pressure.

Interviewer: Noah Baker

And that’s very much what you have been working on here, is trying to design a prosthetic device that could help create this baroreflex in those that have lost some of that function due to spinal cord injury. Tell me about the device you’ve been working on.

Interviewee: Grégoire Courtine

We have an electrode array, so you imagine like a second skin that slides on top of the spinal cord, and the electrodes are very precisely located in order to target the neural circuits that normally regulate blood pressure. And then we have a catheter in the artery that measures the blood pressure constantly in real-time and detects the needs for the blood-pressure modulation. So, these go through a computer, a mini computer, very smart, located in the abdomen, that will deliver electrical stimulation to the spinal cord. And what is very novel here is that the stimulation of the spinal cord, they are so-called biomimetics, in the sense that they reproduce the way the brain stem, our brain, would naturally activate the spinal cord in order to modulate blood pressure.

Interviewer: Noah Baker

You said that your prosthetic is very specifically targeted towards the neurons that work in the system, but trying to work out which neurons those needed to be is actually a whole process in itself. To some extent, that was a bit of a trial and error procedure to get to that point.

Interviewee: Grégoire Courtine

Yes, it’s very difficult, of course, to dissect the specific neurons that are first involved in blood-pressure instability and then second that we are stimulating with our neural prosthetic system. People tend to see the spinal cord as one tube with reflexes and simple circuits, but the spinal cord is a brain in itself, and a lot of functions are distributed throughout the spinal cord. But we are living in an extraordinary time for neuroscience because we have such precise tools to dissect the neurons, the connections. We have been able really to identify a very small region in the middle of the back that has a high concentration of these circuits. We call it the haemodynamic hotspots because when we target this specific region, we have an incredibly higher level of efficacy in the modulation of the blood pressure.

Interviewer: Noah Baker

Okay, so you worked with rat models, then you moved to non-human primates and then you did test your system in a human patient. Tell me about that process because that’s the key moment for any clinical researcher, the first time they get to test their system in a human patient.

Interviewee: Grégoire Courtine

It’s true. It’s a moment I have already experienced when I was working with the recovery of walking, paralysed people making their first steps when we turn on the stimulation, and the same happened with the one patient. So, this is actually a surgeon in Calgary, and we couldn’t test all of the features of the neuroprosthetic baroreflex, so we could only test the basic features, but for him it was sufficient to really dramatically change his quality of life and since then, he has completely stopped medication. He is using the stimulator whenever it’s necessary for him to modulate his blood pressure, and that’s really changed this one aspect of his life as a person with a spinal cord injury.

Interviewer: Noah Baker

I mean, that’s exactly, I suppose, what you as a scientist and a clinical scientist wants to hear with your work. I’m always conscious in these kinds of situations that it’s very rare to find a win that doesn’t have other things to think about. There’s almost always some form of side effect. Are there side effects you’re concerned about? Chronically stimulating these neurons, could they perhaps have impacts on other parts of the body?

Interviewee: Grégoire Courtine

There is a concern that by stimulating constantly or maybe also over-stimulating that you can damage other organs. But also maybe more importantly, you may receive what is called autonomic dysreflexia, which is a very unknown phenomenon, but people with spinal cord injuries are very much aware of it, meaning stimulus – typically a bladder infection or like constipation, for example – will activate the blood-pressure system and elevate suddenly the blood pressure. This could lead to a stroke and people die because of autonomic dysreflexia, so of course there is a concern that by using our stimulation we can facilitate autonomic dysreflexia and this is certainly an aspect we will investigate in the future.

Interviewer: Noah Baker

And so, what’s next for your neuroprostheses? Is it a case of testing in more people or is there more you can do to develop and refine the system that you currently have?

Interviewee: Grégoire Courtine

So, for us, the next steps are two-fold. There will be large clinical trials in the United States in order to really establish a prosthetic system that can be used for older people. And then a second part that is really exciting also, we propose a program to really act very early after the injury, with the same technology but implanted right away to really maximise the management of blood pressure in the first days, weeks, months after the injury and really improve the functional recovery. So, this is a very exciting time for this type of research because we can really foresee one treatment within the next two years for people who are suffering from chronic hypotension and maybe within the next five years, an intervention to help in the very early stages and improve recovery.

Host: Shamini Bundell

That was Grégoire Courtine talking to Noah Baker. You can read more about the synthetic baroreflex in his paper. We’ll pop a link in the show notes.