A new study conducted by a team of researchers at Johns Hopkins, reveals that brain cells notify the rest of the body to summon immune system cells, when the brain is damaged. The researchers utilized mouse models that imitate stroke, trauma and infections in humans for this study.
Scientists were already aware of the communication highway between the immune system and brain, but it is still unclear how the brain transmits signals to the immune system. Immune cells are responsible for defending and protecting the body. However, the brain’s “call to arms” may actually cause more damage than good, when it commands the immune cells to infiltrate the brain. The tenaciousness of these brain cells can potentially damage the brain and lead to chronic inflammation.
The study reveals evidence that astrocytes, a type of immune cell in the brain, releases protein-filled sacks and tiny, fat-like molecules, which travel through the bloodstream directly to the liver. In turn, the liver summons white blood cells (WBCs) to travel to the brain at the site of injury.
“This work describes an entirely new way that the brain talks with the body,” says Norman Haughey, Ph.D., professor of neurology at Johns Hopkins University School of Medicine. “Identifying this pathway has helped us pinpoint ways to impede this process and reduce brain damage brought on by the body’s own excessive immune response.”
Previous studies by other collaborators provided the research team with information about a type of inflammation-promoting molecule, which was released from the brain and aimed directly to the liver immediately following brain injury to dispatch immune cells to the site of injury. However, the identity of this intermediary had been difficult to pinpoint for many years.
Exactly what the signal was and how it was able to travel from the liver to the brain is still unknown. Especially, since blood-brain barriers stop molecules in the brain from entering the rest of the body, which is also responsible from preventing molecules from entering the brain. The researchers concentrated on a hydrolase enzyme called neutral sphingomelinase, known as nSMase2, which is activated by a cytokine interleukin 1-beta (IL-1b), an immune system chemical messenger that promotes inflammation. Sphingomelinases such as nSMase2 plays a major role in cell metabolism, breaking down large, fatty molecules into numerous molecules that are utilized by cells for every day functions.
The researchers utilized mice models that had been genetically modified with brain injury to determine if nSMase2 was involved in talking to the immune system during brain injury. Cytokine IL-1b was injected into the striatum, a nuclei in the basal ganglia of the forebrain. To make a comparison, the researchers injected saline in a similar area of the brain in other mice. Mouse brains were also injected with altenusin, a drug that blocks nSMase enzymes from working, along with the cytokine IL-1b.
Within twenty-four hours, the researchers discovered a large volume of WBCs in tissue samples of the mouse brains near the site of injury, but only in the mice that were injected with cytokine IL-1b. In the mouse brains that were injected with altenusin and cytokine IL-1b the volume of WBCs had dropped by nearly 90 percent. While the findings validated nSMase2’s involvement, it did not reveal how the signal from the brain was able to activate the immune response.
The study was published in the journal Science Signaling on April 13, 2017.