University of Cincinnati neurology experts are presenting research at the International Stroke Conference 2024, Feb. 7-9 in Phoenix, Arizona.
Intracerebral hemorrhages (ICH), one of the most severe types of stroke, are caused when a blood vessel bursts inside the brain and causes bleeding in the brain. Hemorrhagic strokes account for 50% of stroke deaths and can cause high neurological disability.
UC researchers including first author W. Shea Wright, MD, used RNA sequencing to identify two new genetic pathways that are associated with worse outcomes for ICH patients.
“DNA gives us the blueprint, but RNA tells us what’s actively going on,” said Wright, a stroke fellow at the UC Gardner Neuroscience Institute. “RNA sequencing gives us the ability to look at every single genetic change that’s occurring within multiple cell types and then see how those genetic changes compare between patients who have poor outcomes versus those who had good outcomes.”
The researchers took blood samples from 278 patients no more than 15 days after their hemorrhagic stroke. Three months after the stroke, they used a standard scale to grade each patients’ symptoms and functional independence.
“After we determined at three months what group the patients fell into, we were able to look at their baseline whole blood and gene sequencing and see which patients did well versus which ones did poorly,” Wright said.
The first pathway the team found overexpressed in patients with worse outcomes affects blood coagulation and cellular interactions.
“Sometimes patients with ICH can be more prone to developing clots after their hemorrhage, and those patients don’t do as well, so that pathway is interesting for that reason,” Wright said.
The second pathway affects immune system activation through specialized white blood cells called neutrophils, which make neutrophil extracellular traps (NETs). Increased expression of genes involved in making NETs were associated with worse ICH outcomes.
“The body is really good at walling off organisms whenever there’s an infection or something else,” Wright said. “But perhaps when it comes to intracerebral hemorrhage, when it tries to wall off the hemorrhage, that just creates more inflammation and longer or worse tissue repair.”
Wright said the research is still in early stages, with the data gleaned on the two pathways helping generate new hypotheses for further study. Moving forward, the team will look to learn more on how the pathways can be targeted with the long-term goal of developing a drug that improves ICH outcomes.
While clinical trials testing surgical approaches to improve ICH outcomes have been largely unsuccessful, Wright said she is hopeful focusing on genetic changes could be more fruitful.
Subarachnoid hemorrhage strokes (SAH) commonly occur in younger people and are particularly dangerous with a high risk of death. Because of its high mortality rate, stroke researchers have focused on primary prevention of SAH and its acute management.
Researchers at UC led by first author David Robinson, MD, looked at population data from the Greater Cincinnati and Northern Kentucky regions to assess how these interventions have impacted rates of SAH from 1993-2020.
The researchers sorted cases of SAH into two subtypes: aneurysmal and nonaneurysmal. Robinson said because the two subtypes have different causes and outcomes, it was important to look at them separately.
“Aneurysms are weak spots in the blood vessels of the brain and when they cause subarachnoid hemorrhage, the risk of dying is much higher,” said Robinson, assistant professor in the Department of Neurology and Rehabilitation Medicine in UC’s College of Medicine. “Nonaneurysmal subarachnoid hemorrhages are caused by a more diverse number of pathologies and the risk of death tends to be lower.”
The researchers found that aneurysmal SAH strokes are becoming less common and that people with SAH strokes are dying less frequently, while nonaneurysmal SAH strokes appeared to be increasing in frequency.
“This is encouraging evidence at the population level that our interventions have helped reduce the burden of aneurysmal subarachnoid hemorrhage,” Robinson said. “Why nonaneurysmal subarachnoid hemorrhages are becoming more common is unknown and will need to be studied further in future work.”
UC’s Joseph Broderick, MD, will provide an update on enrollment in the FASTEST trial , which is aiming to find the first proven treatment for stroke due to intracerebral hemorrhage, when blood vessels in the brain rupture and cause bleeding in the brain. Broderick said the study continues to recruit patients, with 362 patients enrolled so far.
UC’s Eva Mistry, MBBS, will present a poster on the SISTER trial , testing a new monoclonal antibody treatment for acute ischemic stroke patients who are not treated with traditional clot-busting medication within 4.5 hours of their stroke onset or are otherwise ineligible to receive these treatments.
Mistry will also present a poster on the TESTED trial , a patient-centered trial that will examine the effectiveness of a stroke treatment for patients with a pre-stroke disability, one of the first studies to focus on this population.
UC involvement at ISC includes: