New study reveals how the brain can ‘remember’ inflammation, replay immune and stress responses, pointing to new possibilities for bioelectronic medicine

What if there was a switch in the brain that could turn on or off the body’s physical response to stress? New research from scientists at Northwell Health's Feinstein Institutes for Medical Research has identified a specific brain circuit that acts as a control center for both inflammation and stress responses. Published today in the Journal of Experimental Medicine, the study shows that a specific group of brain cells are capable of controlling inflammation and stress responses. The discovery helps explain why psychological stress can have such powerful effects on physical health – and promise to drive future developments in bioelectronic medicine.

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Dr. Sangeeta Chavan led the study. (Credit: Feinstein Institutes)

This discovery, led by Sangeeta S. Chavan, PhD, professor in the Institute of Bioelectronic Medicine, and Tatyana and Alan Forman Distinguished Chair in Biomedical Sciences, with Okito Hashimoto, MD, PhD, and Tyler Hepler, BS, advances understanding of the intricate connection between the brain and the immune system. While the brain continuously monitors the body’s health and immune responses, the precise neural code that translates immune signals into physiological responses – such as inflammation, fever, changes in heart rate and stress hormone release – has largely remained a mystery. By identifying specific neurons within a critical brain region that integrate immune information and trigger widespread responses, the research opens new avenues for developing bioelectronic therapies for inflammatory and stress-related conditions.

“These neurons act as a shared pathway where immune signals and stress converge,” said Dr. Chavan. “This helps explain why chronic stress can worsen inflammatory diseases and why inflammation and mental health conditions are so closely linked.”

Using advanced neuroscience techniques, the research team focused on interleukin-1β (IL-1β), a key inflammatory molecule. They discovered that IL-1β activates a specific group of neurons in a stress-processing region of the brain that produce corticotropin-releasing hormone (CRH). Direct activation of these neurons in experimental models reproduced the full physiological effects of inflammation while disrupting the circuit blocked many of these responses. Importantly, the same neurons were also activated during psychological stress. Ablation of these neurons protected from inflammation or changes in heart rate in response to stress, even though stress hormones were still present. These findings show that the brain uses distinct but overlapping pathways to control different components of the stress response.

These results also suggest the concept of an “immune engram,” a neural memory of inflammatory experiences, allowing it to rapidly recall and respond to future threats. This discovery has important implications for bioelectronic medicine, a field that treats disease by targeting neural circuits with electrical signals rather than drugs.

“The brain and the immune system are in constant communication, and understanding this dialogue is essential for advancing bioelectronic medicine,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research. “By identifying the neural circuit that connects immune signaling and psychological stress, Dr. Chavan’s discovery opens new possibilities for medical innovation.”

The Feinstein Institutes for Medical Research is the global scientific home of bioelectronic medicine, which combines molecular medicine, neuroscience and biomedical engineering. At the Feinstein Institutes, medical researchers use modern technology to develop new device-based therapies that modulate neural circuits to treat disease and injury. Targeting this newly identified brain pathway may one day lead to new treatments for inflammatory and stress-related conditions.

Building on years of research in molecular disease mechanisms and the link between the nervous and immune systems, Feinstein Institutes’ researchers discovered neural targets that can be activated or inhibited with neuromodulation devices, like vagus nerve implants, to control the body’s immune response and inflammation. If inflammation is successfully controlled, diseases – such as arthritis, pulmonary hypertension, heart failure, inflammatory bowel diseases, diabetes, cancer and autoimmune diseases – can be treated more effectively.

Beyond inflammation, using novel brain-computer interfaces, Feinstein Institutes’ researchers developed techniques to bypass injuries of the nervous system so that people living with paralysis can regain sensation and use their limbs. By producing bioelectronic medicine knowledge, disease and injury could one day be treated with our own nerves without costly and potentially harmful pharmaceuticals.

About the Feinstein Institutes
The Feinstein Institutes for Medical Research is the home of the research institutes of Northwell Health, the largest health care provider and private employer in New York State. Encompassing 50+ research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its six institutes of behavioral science, bioelectronic medicine, cancer, health system science, molecular medicine, and translational research. We are the global scientific leader in bioelectronic medicine – an innovative field of science that has the potential to revolutionize medicine. The Feinstein Institutes publishes two open-access, international peer-reviewed journals Molecular Medicine and Bioelectronic Medicine. Through the Elmezzi Graduate School of Molecular Medicine, we offer an accelerated PhD program. For more information about how we produce knowledge to cure disease, visit http://feinstein.northwell.edu and follow us on LinkedIn.

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