University of Vermont

Cipolla Identifies Impact of Stroke-Induced Blood Substances on Healthy Vessels

Marilyn Cipolla, Ph.D., UVM Professor of Neurological Sciences (Photo: UVM COM Design & Photography)

Stroke – it’s the leading cause of serious long-term disability and a leading cause of death in the U.S., so figuring out how it affects the entire body is critical to identifying treatments to reduce its negative impact.

Most strokes – about 87 percent of all cases – are ischemic, which means they are caused by a blocked blood vessel. This blockage not only injures the brain, but also triggers inflammation and the release of stress-related substances into the blood. A team of University of Vermont neurological scientists was curious about how those substances might affect the blood vessels in the brain that were not directly impacted by the stroke and elsewhere in the body. The results of their research, published recently in the journal Translational Stroke Research, found that healthy blood vessels became more constricted when filled with serum from the blood of ischemic stroke patients.

“Nobody’s done this before,” says Marilyn Cipolla, Ph.D., UVM professor of neurological sciences, who conducted the study with Isabella Canavero, M.D., a neurology resident from Pavia, Italy, and Helene Sherburne, a Dartmouth College student. Both spent six months in Cipolla’s lab at UVM conducting this focused investigation.

“It is a very simple idea of asking these very simple questions about circulating factors in post-stroke patients,” Cipolla says.

The researchers used serum obtained from three subtypes of ischemic stroke patients: those with large vessel disease; those with large vessel disease with high blood pressure; and those with cardioembolic stroke – a type of ischemic stroke in which the clot originates in the heart and migrates to the cerebral vessels – as well as high blood pressure. Serum that was taken at 24 hours post-stroke was perfused into healthy rat blood vessels. The effect of serum from these different stroke patients was compared between blood vessels from the brain (cerebral) and gut (mesenteric).

Serum from all three types of stroke patients – compared against a control of a normal saline solution – caused the cerebral arteries to constrict or increase in tone, which could potentially reduce blood flow. Brain vessel tone increased the most with the serum from the patients with cardioembolic stroke. To a lesser degree, tone increased in the gut vessels with serum from the patients with cardioembolic stroke and large vessel disease without hypertension.

“The clinical significance of the vasoactive effect of stroke serum in non-ischemic vessels is not clear and may contribute to either clinical improvement or deterioration,” the study authors write.

To learn more about this phenomenon, Cipolla believes further research should explore the characteristics of the serum that cause the increase in tone and whether it negatively impacts outcome. Scientists also could look at the significance of this change, how these circulating factors affect blood flow in the other regions of the brain unaffected by the stroke, and perhaps uncover ways to minimize that effect.

“So, if a vasoconstricting agent is being produced,” Cipolla says, “we could probably inhibit it with therapies.” However, she adds, whether these factors are detrimental due to reducing blood flow in normal tissues, or beneficial due to helping in the repair process is not known, but may be important to understand for future therapies.