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A sudden restriction of blood flow to the brain. That’s how scientists have traditionally explained why people faint.

But several mysteries remain: What causes someone’s blood flow to spontaneously change? And what parts of the brain play a key role?

New research in mice, published this week in the journal Nature, offers a closer understanding of the underlying mechanisms behind fainting.

The researchers theorize that the activation of neurons that link the heart and brain can induce a fainting spell.

“This is the first step to show there is much more to fainting than just reduced blood flow,” said Vineet Augustine, an assistant professor of neurobiology at the University of California, San Diego, and one of the study’s authors.

“The blood flow reduction does play a role, but there are other brain circuits at play here,” he added. “It is not as simple as what cardiology textbooks would say.”

Specifically, the researchers found that neurons below the skull send signals from the heart to the brain that trigger a drop in heart rate, blood pressure and breathing rate. That, in turn, may lead to the most common type of fainting — what scientists call “reflex syncope” — which can result from dehydration, the sight of blood or long periods of standing.

“Oftentimes we’re just scratching our heads as to what to do about it,” said Dr. Zachary Goldberger, a cardiologist at the University of Wisconsin-Madison School of Medicine and Public Health who wasn’t part of the new research.

“Now that these scientists have helped us to understand that there’s a possible mechanism for it, you could potentially imagine that there’ll be therapies on the horizon,” he said.

The findings don’t apply to fainting caused by underlying heart problems such as extremely slow or fast heart rhythms. Those instances are rarer and more deadly, Goldberger said.

A fainting experiment in mice

Going into the study, the researchers speculated that fainting was caused by activation of the vagus nerve — a superhighway of neurons, or nerve cells, that connects the brain to other organs.

The vagus nerve is part of the parasympathetic nervous system, which helps the body rest and relax. Scientists suspect that when people faint, their parasympathetic response becomes exaggerated, so their heart rate, blood pressure and breathing slow down too much.

To find out what role the vagus nerve might play in fainting, the researchers examined the internal organs of mice under a microscope. From there, they identified a specific stretch of neurons in the vagus nerve that travel from the lower chambers of the heart to the brainstem, or bottom part of the brain.

“Each neuron has two branches,” Augustine said. “One branch goes to the heart and the other branch goes to the brainstem. So it picks up signals from the heart and then it relays it onto the brainstem. It really forms a nice bridge.”

Next, the researchers tested whether stimulating these specific neurons in mice could induce fainting.

“We have this little fiber which we put into their brains, and we can shine just a little tiny bit of blue light to activate these neurons,” said Jonathan Lovelace, a staff research associate in Augustine’s lab and co-author of the study.

Once the neurons are activated, “these mice will maybe walk around for five seconds, and then spontaneously fall over and become still,” Lovelace said. “After a few more seconds, they’ll get back up and start walking around.”

The mice exhibited other classic signs of fainting in humans: Their blood pressure, breathing and heart rates went down, their pupils dilated and their eyes rolled back into their heads.

“We were able to replicate this typical, iconic eye roll,” Augustine said. “That also very tightly correlated with the time when the fainting episode happened.”

The researchers also noticed that activating the neurons constricted blood vessels and reduced blood flow from the heart to the brain — two more characteristic signs of fainting.

But Augustine said there’s more to learn. His team still doesn’t know what activates the nerve pathway in real life, or whether the findings neatly translate to humans.

“There would be much more nuance to human fainting,” he said.

What causes fainting in humans?

Prior to the new research, scientists understood that people faint when there’s not enough blood entering or exiting the heart, cutting off blood flow to the brain.

“You’re not going to get blood to the rest of your body, including your brain, and you’ll pass out,” said Dr. Shamai Grossman, an associate professor of emergency medicine at Harvard Medical School who wasn’t involved in the study.

Most of the time, fainting isn’t worrisome unless someone passes out while driving or injures themselves during a fall, Grossman said. Roughly 40% of people have a fainting spell in their lifetime, often triggered by something minor.

“When you’re standing for a long period of time or when you’re thirsty, blood kind of pools in your legs, or in pregnant women when the fetus exerts pressure on your chest, it prevents blood from flowing back into the heart,” Augustine said. “Same thing when you have beginners playing musical instruments. They exert a lot of pressure on the chest and you tend to have fainting episodes.”

Other people faint from emotional responses to hearing bad news or even something funny — most likely because their body over-activates their parasympathetic nervous system to calm them down.

While doctors currently don’t have ways to prevent spontaneous fainting spells, Augustine said targeting the neurons identified in his study could be one approach. For instance, doctors could remove or replace certain genes involved in the vagus nerve pathway.

“In the future when things like gene therapy or targeted nerve stimulation become more pronounced in humans, you now have targets to potentially probe,” he said.

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