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Scientists at the University of California, San Diego have discovered a pathway between the brain and the immune system that could lead to new ways to alleviate heart attacks. They showed that disabling specific parts of that circuit could significantly improve the outcome of mice with experimentally induced heart attacks.

‘The damage almost disappeared,’ says the UCSD neuroscientist. Vineet Augustinewho led the new study Published in the magazine on Tuesday cell.

Although it may not seem obvious how neuroimmune crosstalk relates to heart disease, the connection between the nervous and immune systems has fascinated researchers for decades. Some researchers focus on the vagus nerve, a giant bundle of fibers that transmits signals between the brain and other organs to control breathing, blood pressure, digestion, and other involuntary functions.

A key discovery came in 2000, when researchers at the Feinstein Institute for Medical Research on Long Island, New York, showed that electrically stimulating the vagus nerve in rats suppressed the production of immune proteins that cause inflammation.

Last July, embedded type vagus nerve stimulator SetPoint Medical — Developed by a company co-founded by Drs. Kevin Tracydirector of the Feinstein Institute — has received FDA approval as a treatment for patients with the autoimmune disease rheumatoid arthritis.

Previous research had also found significant connections between the cardiovascular system and the nervous and immune systems. The day of the devastating Northridge earthquake in 1994, sudden cardiac death In Los Angeles County, the number rose more than fivefold. Similar spikes occur at high-stakes sporting events. During stressful moments, our heart rate spikes to protect us.

“The brain says, ‘Hey, get up and run, you’re going to die,'” he says. Kalyanam Shivkumara cardiac electrophysiologist at UCLA.

These fight-or-flight signals are helpful in emergencies, but in the long term they cause harmful inflammation. “Then the heart swells. Arrhythmia and heart failure occur.” new anatomy atlas of the heart.

Current research at UCSD is using cutting-edge tools in genetics and neuroscience to better understand how the brain communicates with the heart and the brain’s role in heart attacks.

This shows how the vagus nerve carries signals between the brain and heart. Dr. Augustine said they discovered that when mice suffer a heart attack, certain vagus nerve neurons (TRPV1-expressing neurons) “literally wrap around the injury site.” His team thought that by blocking communication through these nerve cells, they might be able to slow or prevent heart attacks in laboratory animals.

It was a bold idea. When Augustine talked about the early stages of the project four or five years ago, some scientists would tell him it was “unrealistic.”

The experiment was technically demanding and required multiple researchers working together for long periods of time. One performed heart surgery on mice, another targeted specific cells in the brain, and other researchers took physiological measurements and performed echocardiography, which images the heart in real time.

Saurabh Yadav, a postdoctoral fellow in Augustin’s lab and one of the paper’s first authors, said in an email that “a minor error at any step can derail the entire experiment.” “There were moments where I wondered if I had taken on too much, or if it was simply too big of a leap.”

Then came an “incredibly heartening” moment, Yadav told NPR. The research team turned off this small group of TRPV1 neurons and saw significant improvements in pump efficiency and electrical signals associated with heart contraction. And that was the very first victory.

TRPV1 neurons transmit signals from the heart to the hypothalamus, a deep brain structure that regulates body temperature, thirst, hunger, and sleep. Other cells in the hypothalamus receive these signals and relay them to another group of nerve cells, which release immune proteins that travel back to the heart and cause inflammation. Blocking one of three junctions in the heart-brain-immune loop reduced heart attack complications in mice, the UCSD team reports. cell.

“The findings of this paper are very impressive,” he says Cameron McAlpineis a neuroimmunologist at the Icahn School of Medicine at Mount Sinai but was not involved in the new study.

McAlpine said that while it has long been known that heart attacks cause major changes in the immune and nervous systems, it’s only in the last five or six years that researchers have developed “the tools and techniques that allow us to study this at a really deep level,” including genetic approaches to precisely manipulate the activity of specific groups of nerve cells.

Augustine says research in this area has been stalled for years because of a conceptual divide: the idea that the brain is a command center that sends signals to other parts of the body. Clinicians “were focused on the organs themselves, but the nervous system seemed to be ignored,” he added. “That created a lot of silos.”

Currently, there is increasing interest in the nervous and immune systems. These systems “affect virtually everything in the body,” he says. “This field is really exploding.”

It will still be years before the mouse discovery enters human clinical trials, but further research could prove that approved vagus nerve stimulators are useful for heart attacks, the researchers say. Asha Rollsa neuroimmunologist at Tel Aviv University in Israel. her team is brain reward network Inflammation in mice can be modulated in a variety of situations, including not only heart attacks but also bacterial infections and cancer.

In future experiments, Augustine says his team will flesh out the heart-brain-immune circuit by studying, for example, what exactly neurons sense and how they communicate with heart cells.

In a 2024 paper, McAlpine et al. found that a heart attack sends immune cells to the brain. promote deep sleep.

A growing body of research shows how the brain-immune connection manifests differently depending on the condition, and is “likely to be much more complex” than the specific pathways each research team has identified, Rawls told NPR in an email. Each manipulation can affect many other pathways such as blood flow, angiogenesis, and metabolism. A National Institutes of Health program called Stimulation of peripheral activity to relieve the condition (SPARC)) is funding research to stimulate neural circuits to alleviate disease.

Shivkumar sees an emerging theme. “The message people should get is, oh my God, scientists are doing something very exciting, but we’re literally building on ancient knowledge,” he says. Research on vagus nerve stimulation supports what Buddha said: Meditate. I call it Zen cardiology.