Immune Cells Recruited for Stroke Recovery

Neutrophil-related proteins may protect the brain against damage and disability from intracranial hemorrhagic stroke.

Immune cells are known to fight against numerous pathogens and protect the body against various diseases. A new study published by Nature Communications suggests that neutrophils may also play a role in healing the brain after a stroke.

The authors found that 2 neutrophil-related proteins may ward off stroke-related damage and could be used to treat intracerebral hemorrhage therapy.

“Intracerebral hemorrhage is a damaging and often fatal form of stroke for which there are no effective medicines,” said senior author Jaroslaw Aronowski, MD, PhD. “Our results are a hopeful first step towards developing a treatment for this devastating form of stroke.”

Intracerebral hemorrhage is a form of stroke that occurs when blood vessels rupture. It accounts for up to 15% of all strokes and can lead to mortality or disability.

Previous research suggests the neutrophils are the first to respond to hemorrhages and the immune cells may both hurt and heal the brain.

In the current study, interleukin-27 (IL-27) was found to transform the role of neutrophils from harming the brain to healing it.

The authors discovered that injections of IL-27 helped mice recover from an intracranial hemorrhage, according to the study. After treatment, mice had improvements in mobility, while mice treated with an IL-27 inhibitor had slower recovery.

IL-27-treated mice were also observed to have less brain damage, swelling, and lower levels of iron and hemoglobin, which can be toxic at increased levels, according to the study.

“This study shines a spotlight on the critical role the immune system may play in helping the brain heal after a hemorrhage or stroke and opens new avenues for stroke treatment strategies,” said Jim Koenig, PhD, program director at the National Institute of Neurological Disorders and Stroke.

When the body sustains an injury, neutrophils invade the site and release germ-killing substances. The authors found that this occurs within minutes of a hemorrhagic stroke.

The authors suggest that the brain secretes high levels of IL-27 after a stroke, which results in a second response of neutrophils and healing substances. After 1 hour, IL-27 levels were found to increase in the brain and blood for 3 days and peaked after 24 hours, according to the study.

Additional research revealed that microglia brain cells produced IL-27 as a response to red blood cells. Once released, the molecules traveled to the bone marrow and altered the role new neutrophils play.

When new neutrophils were harvested from mice and treated with IL-27, the immune cells had increased activity in lactoferrin—a healing gene—and diminished activity of genes that kill cells. Treating mice with an IL-27 antibody reduced the amplification of lactoferrin, according to the study.

“Our results suggested that IL-27 links the brain to the bones,” Dr Aronowski said. “We can use these results as a source for ideas for developing potential treatments for hemorrhagic stroke.”

The authors also found that lactoferrin may protect against intracerebral hemorrhage. Rodents injected with lactoferrin 30 minutes after a stroke had increased recovery and lower levels of brain damage compared with placebo, according to the study. This treatment was found to be effective for up to 24 hours.

The authors are now planning to test lactoferrin in human patients.

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