Preventing mesh network from clogging blood vessels may improve stroke outcomes

Studies in mice have shown that preventing the formation of a sticky mesh that forms in blood vessels after a stroke can protect the brain and lead to better outcomes for patients

Stroke is the leading cause of disability in the United States

But according to the new study, the cells carried by the backflowing blood could cause further damage

"These meshwork structures cause more brain damage by trapping other cells, reducing blood flow and clogging blood vessels (in the brain)," said the study's senior author, Dr.

Campbell and his colleagues found that they could prevent these effects in a mouse model of stroke by administering a mesh-blocking compound to the animals

"We urgently need new treatments for ischemic stroke," said Jennifer Mayeske, MD, professor of neurology and stroke expert at U of U Health and co-author of the study

Beneficial defenses also do damage

NETs are part of the immune system's defense against pathogens

The team first looked for signs of NETs in the brains of stroke patients

"They are able to trap many other cells and potentially reduce blood flow into the tissue and oxygen into the brain," Campbell said

When the team analyzed blood samples from patients treated for ischemic stroke at U University Health, they found more evidence that NETs may negatively affect stroke patients

These observations prompted Campbell and postdoctoral researcher Frederick Denom, PhD, the study's first author, to return to the lab to study how NETs form after stroke

"We really think that when the blood initially returns to the brain, it's when you activate the platelets, and then those platelets deactivate the neutrophils," Campbell explained

Blocking the network protects the brain

While the role of NETs in stroke is troubling, it also hints at an opportunity for intervention

Encouragingly, the treatment improved outcomes not only in young, healthy mice, but also in older mice and mice with diabetes

The nNIF peptide, which is currently being developed as a potential sepsis treatment, may also help reduce stroke damage to patients, Cambell said
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Once reticulocytes are formed, the peptide cannot prevent the formation of reticulocytes, but the findings in mice suggest that there may be a window of opportunity during which the formation of toxic reticulocytes can be intervened and prevented
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More studies are needed to further evaluate the role of nNIF in animal models of stroke before it can be determined whether nNIF is suitable for clinical trials in this context
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