Researchers believe strokes are further complicated when the immune system "goes rogue," but what if we could block the immune pathway? A new study suggests we may be able to do just that in mice to improve long-term outcomes after a stroke.
Ischemic strokes, the most common type of stroke, are caused by a blocked blood vessel in the brain. Previous research has found this type of blockage to be associated with inflammation that can further damage brain tissue. Now, researchers have observed in mice a naturally occurring protein that blocks an inflammatory immune response to aid stroke recovery.
The study was led by University of Utah postdoctoral researcher Frederik Denorme, Ph.D., and presented at the American Heart Association’s Vascular Discovery: From Genes to Medicine Scientific Sessions 2021.
“By studying people who had an ischemic stroke and mice subjected to ischemic stroke, we discovered that during stroke, the immune system goes rogue in the brain,” Denorme said in a statement.
Efforts to develop new treatments to reduce inflammation related to strokes have been largely unsuccessful in the past, Denorme said.
The study focuses on neutrophils, a type of immune cell that floods in to repair damaged areas when infections or inflammation occur in the body in both humans and mice. Inflammation prompts proteins to form neutrophil extracellular traps (NETs) to prevent infections and capture germs. However, researchers have found that during a stroke, NETs can cause blood clots and brain damage when they occur in the absence of infections.
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Denorme's study included 27 people with stroke and 27 healthy blood donors who served as a control group, all with an average age of 60. The control group members were less likely to have NETs and showed a lack of certain proteins in the blood. The biomarker was highest in people with stroke who died or survived but now have a disability.
To study whether NETs could impact stroke recovery, the research team turned to mice. NET formation was blocked in mice by administering nNIF, or neonatal NET-inhibitory factor, a naturally occurring protein found in human umbilical cord blood.
Mice who received nNIF had reduced brain injury, improved neurological and motor function and enhanced survival after stroke.
“The degree of protection provided by the nNIF protein exceeded our expectations and makes us really excited about a future where NET inhibition may significantly improve stroke outcomes,” Denorme said.
Researchers have yet to translate these changes into humans, and some challenges to testing the idea will be finding enough patients and figuring out the timing for administration of the treatment.
“It will be exciting to see whether further studies confirm the findings for inhibition of NET formation and provide a rationale for clinical trials testing this novel approach," said Mitchell Elkind, M.D, past president of the American Heart Association.