Scientists shift function of neutrophils to heal brain after hemorrhages

Scientists have taken the next steps in finding a treatment for intracerebral hemorrhages, a type of stroke that results in 30- to 67-percent mortality rates and poor prognosis, a current study in Nature Communications states.

The team of seven researchers who worked on the study hypothesized that intracerebral hemorrhage (ICH) induces the production of interleukin-27 (IL-27), an immunoregulatory protein that triggers the production of polymorphonuclear neutrophils (PMN) in the bone marrow. Within hours of a stroke, PMNs—the immune system’s shortest-lived, most abundant cells—rush to the brain, where they release microbial defense-related molecules that have been known to aggravate ICH conditions. The study’s authors focused, however, on a subset of molecules released by PMNs that can be beneficial to a brain suffering from ICH by sequestering haptoglobin and lactoferrin, a healing gene.

Lead author Jaroslaw Aronowski, MD, PhD, and colleagues believed the introduction of IL-27 at the PMNs’ native site—bone marrow—could help shift the neutrophils’ function from negative to positive before they accumulate in the brain after a stroke and release their chemical-filled granules. PMNs are generally among the first blood cell types to enter the brain after a stroke and continue to infiltrate damaged tissue for up to several weeks after ICH onset, the study’s authors wrote.

The researchers wrote in their study that IL-27 is triggered by red blood cells and released in large amounts after ICH strokes, which then leads to a second wave of PMNs arriving at the hemorrhage site. In test mice, Aronowski and co-authors found IL-27 levels climbed and remained high an hour after hemorrhage struck, remaining at those levels for around three days.

The IL-27 released after ICH then appeared to make its way to the bones of the mice after the stroke, the authors wrote, heading straight for the marrow, where it converted PMNs into more helpful neutrophils that could mitigate blood overflow in the brain. When the scientists specifically treated PMNs with IL-27, they found the chemical increased lactoferrin in the neutrophils and stalled the cell-killing components of the granulocytes.

In a release from the National Institute of Neurological Disorders and Stroke, Aronowski said it appeared the IL-27 “links the brain to the bones,” opening possibilities of using these chemical actions to treat hemorrhagic stroke and control blood flow in the brain after ICH.

Aronowski and colleagues also injected mice and rats with lactoferrin 30 minutes after ICH and found those rodents recovered faster than ones who didn’t receive the same treatment. Injecting lactoferrin 24 hours after a stroke still proved useful, they wrote in the study.

“Lactoferrin appears to have a long treatment window,” Aronowski said in the release. “This means lactoferrin might one day be used to help patients recover from intracerebral hemorrhage.”