Brain Stimulation Can Alter Immune Response by Targeting Vagus Nerve

Researchers at the Feinstein Institutes for Medical Research — the global scientific home of bioelectronic medicine — discovered that a small cluster of neurons within the brain is responsible for controlling the body’s immune response and the release of cytokines, which leads to inflammation in the body. This discovery, published yesterday in Proceedings of the National Academy of Sciences of the United States of America (PNAS), adds to the growing body of research in the field of bioelectronic medicine and, more specifically, how the brain regulates the body’s immune response.

Bioelectronic medicine is the scientific field exploring the use of electronic devices to treat diseases and injury instead of drugs while reducing significant side effects associated with drugs. The goal of bioelectronic medicine is to identify neural targets that can be selectively activated or inhibited when needed; that in turn, control the function of specific organs.

One area of study is how the vagus nerve, the longest nerve in the body that controls the physiology of organs like the heart, the intestines, and the liver, can be targeted to treat conditions like heart failure, hypertension, rheumatoid arthritis and lupus. Once neural targets are identified, scientists and engineers can build bioelectronic devices to modulate the activity of that neural target.

This new research, led by Sangeeta S. Chavan, PhD, professor at the Feinstein Institutes, reveals a population of neurons in the brainstem dorsal motor nucleus (DMN) of the vagus are responsible for communicating cytokine-inhibiting signals to the splenic nerve. By controlling these neural signals through selective stimulation, researchers can turn off cytokines and other proteins that affect the body’s immune response, which accounts for many inflammatory diseases and autoimmune disorders.

“Think of the vagus nerve as the body’s main highway that helps control the immune system. Sometimes, you can’t slow it down which causes over-inflammation and disease,” said Dr. Chavan. “With this discovery, we are pleased to note that we can target different neural sites such as the brain, the splenic nerve and the vagus nerve, using bioelectronic devices to control inflammation and treat illness without pharmaceuticals.”

Neural signals are sent through vagus nerve fibers in an afferent (toward the brain) or efferent (away from the brain, toward peripheral organs) direction. To identify the vagus fiber subsets and the brain regions, Dr. Chavan and Adam Kressel, MD, a graduate student in Dr. Chavan’s lab, used a combination of anatomical and functional mapping with direct assessment of the immune response. Using bioelectronic devices, specifically laser light to activate neurons as well as microcuff electrodes to record neural activity, their research showed that selective activation of a subset of vagus nerve fibers stemming from the brain are able to control the immune system response to inflammation.

“Dr. Chavan’s research helps us connect the activity between the brain, the vagus nerve and other organs, giving us a better understanding of the source that controls inflammation,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes. “We will continue to make progress in the field of bioelectronic medicine so that the most devastating diseases can be treated more effectively, and without the use of drugs.”

Reference:

Kressel AM, Tsaava T, Levine YA, et al. Identification of a brainstem locus that inhibits tumor necrosis factor. PNAS. Published online November 9, 2020. doi:10.1073/pnas.2008213117

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