The Neural Tourniquet

Daniel Powell [00:00:03]:
I want to kick off today with a question to Navid. What is the coolest therapy name you've ever heard?

Navid Khodaparast [00:00:09]:
Oh, by far, it's the neural tourniquet.

Daniel Powell [00:00:11]:
The neural tourniquet. So, we're going to talk about the neural tourniquet today. A 25-year endeavor at this point in time that we're pioneering? Not us the whole time, but many scientists over the years. So, what is it?

Navid Khodaparast [00:00:24]:
I remember that time I was in grad school doing experiments in the lab and someone said, “Hey, did you see this study from Kevin Tracy’s group?” They showed that VNS can stop bleeding. And they called it the neural tourniquet. Coolest name ever. The vagus nerve can stimulate almost every organ system, and Tracy’s group at the Feinstein Institute focused on what happens when you stimulate it below the brain—particularly the gut and spleen.

Navid Khodaparast [00:01:04]:
They were originally studying inflammatory stress—how vagus nerve stimulation could reduce systemic inflammation caused by hormones and cytokines. Instead of anti-inflammatory medications or steroids, they asked: what if we use the nervous system to reduce inflammation? That kicked everything off.

Daniel Powell [00:02:03]:
When you first heard about this, did you believe it? I thought, “That’s stupid.” But I’m not the scientist.

Navid Khodaparast [00:02:13]:
I knew the lab’s work was credible. Inflammation being controlled by the nervous system is well known. Septic shock is a neural response. But the discovery was a eureka moment—they didn’t initially realize that stimulating the vagus would affect platelets via the same pathway that reduces inflammation through T cells.

Alejandro Covalin [00:03:21]:
And the neurotransmitter involved in the spleen is actually norepinephrine, not acetylcholine like most parasympathetic responses. So, you get a sympathetic-like effect—activating the T cells.

Daniel Powell [00:03:52]:
In human terms, the neural tourniquet changes platelet behavior. We’ve seen studies show a 50% reduction in blood loss and a 50% reduction in clot time. That’s huge.

Navid Khodaparast [00:04:13]:
Exactly. This is 20 years of preclinical work on improving hemostasis—reducing blood loss. That’s the goal of every surgeon and anesthesiologist.

Alejandro Covalin [00:04:34]:
Rather not lose any blood.

Navid Khodaparast [00:04:36]:
Right. Early studies used small injury models—just 1 to 5 minutes of vagus nerve stimulation led to a 50% blood loss reduction. That’s incredible.

Daniel Powell [00:05:10]:
I was fascinated learning about the clotting cascade—the chain of chemical events that ensures platelets only clot at the wound site and not elsewhere. The system is brilliant.

Navid Khodaparast [00:05:46]:
The clotting factors are key to making that work. If you’re missing one, you get bleeding disorders.

Daniel Powell [00:06:00]:
Like hemophilia—specifically, missing factor VIII.

Alejandro Covalin [00:06:05]:
Or factor IX, or factor XI. Each one amplifies the response.

Navid Khodaparast [00:06:23]:
Which is why the Nature paper was so important. They tested this in healthy and hemophilic mice—and found it worked in both. That’s a massive discovery for bleeding disorders globally.

Daniel Powell [00:06:58]:
So, 20 years of animal studies at Feinstein. They approached us to take it to market. But we had two big transitions: animal to human, and implanted cervical vagus to our wearable ear device. Those are major jumps. How did we prove it works?

Navid Khodaparast [00:07:38]:
The neural tourniquet demands a non-invasive solution—something practical and fast to apply.

Alejandro Covalin [00:07:48]:
And fast to apply.

Navid Khodaparast [00:07:49]:
Exactly. Our challenges were translational: animal to human, and invasive to non-invasive. Fortunately, there’s plenty of data showing ear stimulation affects heart rate, gut motility, and inflammation—so we knew signals were reaching the brain and traveling through the vagus.

Daniel Powell [00:08:18]:
And spleen control of inflammation was key.

Navid Khodaparast [00:08:22]:
Right. So, does it translate to humans? That’s the big question. Animals in labs are pristine. Humans aren’t. They smoke, drink, don’t sleep—we can exclude for some, but not all variables.

Alejandro Covalin [00:09:03]:
Lab rats sleep eight hours a night.

Navid Khodaparast [00:09:07]:
Exactly. Real-world humans are complex. But we believed our tech could handle it. So, we ran our first study.

Alejandro Covalin [00:09:27]:
We started with healthy humans to see if platelet physiology would change. And yes—it did. We took blood before and after stimulation and saw changes in the platelets themselves.

Navid Khodaparast [00:09:58]:
We returned to Feinstein—they had the expertise, and they were the first to show vagus modulation of platelets. Using flow cytometry, we looked at how the platelet surface changed—its phenotype. That’s how we measure if they’re “primed” to clot.

Navid Khodaparast [00:11:23]:
With just 30 minutes of ear stimulation, we saw those changes. The platelet phenotype changed. We haven’t published it yet, but the data is strong.

Daniel Powell [00:11:29]:
So how long do the changes last?

Navid Khodaparast [00:11:39]:
In our study, about two hours. In animals, they saw effects lasting two days.

Alejandro Covalin [00:11:53]:
And in humans, platelets live 7–10 days, so the effect might last longer than what we measured.

Daniel Powell [00:12:24]:
Why are we confident there are no adverse events?

Navid Khodaparast [00:12:31]:
Look at the safety profile of vagus nerve stimulation—used for 30+ years. People live healthy lives with implanted stimulators. No strokes, no hypocoagulability. It’s incredibly safe.

Daniel Powell [00:13:03]:
Our biggest challenge now is choosing where to go next. We could apply it pre-surgically, on the battlefield, for postpartum hemorrhage—or for bleeding disorders. It’s not a huge population, but they desperately need something. We might have a treatment that could help every person in the world with a bleeding disorder.

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