Natural protein associated with better recovery after stroke in mice

A naturally occurring protein that blocks an inflammatory immune response has been linked to better recovery from stroke in a study in mice, according to preliminary research to be presented to the American Heart Association’s Vascular Discovery: From Genes to Medicine Scientific Sessions 2021. The virtual meeting is September 22-24, 2021, and is a leading global exchange on the latest advances in new and emerging scientific research in the fields of arteriosclerosis, thrombosis, biology vascular, peripheral vascular disease, vascular surgery and functional genomics.

By studying people with ischemic stroke and mice with ischemic stroke, we found that during stroke, the brain’s immune system goes down. Previous research has shown that this most common type of stroke, caused by a blocked blood vessel in the brain, is associated with inflammation which can further damage brain tissue. In the past, however, treatments aimed at reducing this inflammation were unsuccessful. “

Frederik R. Denorme, Ph.D., senior study author and postdoctoral researcher, University of Utah

In this study, Denorme and his team looked at a particular immune cell, called a neutrophil, in humans and mice. The usual role of neutrophils is to prevent infections caused by viruses and other germs, in part by forming a web-like structure, or NET, for an extracellular neutrophil trap, to capture the germs. Researchers have found that during stroke, however, NETs can occur in the absence of infection and, instead of being protective, can cause blood clots and brain damage.

Compared to a control group of healthy people without stroke, people with stroke were more likely to have NETs, ​​as evidenced by the presence of certain proteins in the blood. These biomarkers were highest among people with stroke who died or survived with a disability. Study participants included 27 people with stroke and 27 healthy blood donors at the University of Utah. Adults were on average 60 years old, the majority were white and 40% were women.

To study the effects on stroke, the researchers blocked the formation of NETs in mice. To block NET formation, they administered a natural protein called nNIF, for neonatal NET inhibitory factor, found in human umbilical cord blood.

Mice pretreated with nNIF exhibited reduced brain damage, improved neurological and motor functions, and improved survival after stroke. Additionally, nNIF further improved stroke outcomes when administered after stroke onset and blocked NET formation after stroke without affecting other critical functions of neutrophils.

“The degree of protection provided by the nNIF protein has exceeded our expectations and makes us really excited about a future where inhibition of NET can dramatically improve stroke outcomes,” Denorme said. “It’s important to note, however, that more research is still needed and is currently underway to see how we can translate these lab-to-stroke clinic results to help improve outcomes for people after stroke. “

One limitation of the study is the small number of human stroke patients. Future studies involving more people are needed to verify the results of the study and to determine the optimal timing for nNIF treatment, after further studies in animal models establish its effectiveness.

“It has become increasingly clear that immune mechanisms play a role in brain damage and long-term outcomes after stroke. So far, strategies to mitigate these immune pathways have worked in animals, but we haven’t been able to translate these changes into human success, perhaps because the immune pathways have effects on both beneficial and harmful, ”said Mitchell SV Elkind, MD, MS, FAHA, FAAN, past president of the American Heart Association and professor of neurology and epidemiology at Vagelos College of Physicians and Surgeons and assistant neurologist at the New York-Presbyterian / Columbia University Irving Medical Center. “It will be exciting to see if further studies confirm the results of inhibiting NET formation and provide a rationale for clinical trials testing this new approach.”

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