A New research grant will enable researchers develop a better understanding of inflammation in stroke and how it affects the recovery of stroke patients.
Kyle Walsh, the principal of investigator of the CAPSTONE study and his team at the University of Cincinnati have received a five year, $2.5 million grant from the National Institute of Neurological Disorders and Stroke (NINDS).
CAPSTONE is an acronym for Central and Peripheral STrOke and inflammatioN with Exosomes.
This research focuses on patient recovery after intracerebral haemorrhage (ICH), which is caused by a blood vessel in the brain rupturing.
Though ICH strokes only account for an estimated 20 per cent of all strokes, they are often deadly and cause severe disability.
Walsh says that the brain suffers injury from the bleeding itself during an ICH stroke, known as “primary injury,” but following this a number of inflammatory processes occur both inside the brain and in the circulating blood.
Previous research suggests that while some of these inflammatory processes help repair the damage, others are harmful and contribute to a “secondary injury.”
Daniel Woo, who is co-investigator of this study, says that in some circumstances inflammation can persist and become chronic in the brain long after it has done its ‘job’, this is believed to lead to neurodegeneration.
Almost 40 per cent of patients who survive an ICH stroke develop progressive cognitive decline within a few years of the strokes occurrence, which is so bad it can be comparable to dementia.
Methodology
In this study, the researching team will analyse differing inflammatory biomarkers to see which are associated with positive outcome and which are tied to poor outcomes in patients.
On methodology, Walsh says: “So we’ll be using the blood and plasma samples from those patients to look at a number of different mediators of inflammation.”
The mediators used will include these main categories: gene expression (messenger RNA or mRNA), specific types of RNA called microRNA and exosomes, these are essentially small pieces of cells that travel between or communicate from one cell to another.
Patient samples are to be obtained from Woo’s ROSELAWN grant, which is recruiting 500 ICH patients and 250 of those will be followed long term.
On methodology, Walsh says: “Many studies may only follow patients for three months or six months after stroke. ROSELAWN actually follows patients much longer, up to a few years after the ICH, to look for clinical outcomes as well as long-term cognitive decline.”
Identifying what inflammatory processes were incurring in the brain during stroke recovery was previously difficult as researchers were limited in methods, to only being able to draw blood and then examining the occurrences in the larger bloodstream.
Now, thanks to new technology, testing this same circulating blood provides an opportunity to identify biomarkers from inside the brain.
Walsh highlights that this is because exosomes released from brain cells into the circulating bloodstream can be tagged and isolated. The microRNA inside the exosomes can the be characterised.
Woo says: “We can look at the inflammation that’s occurring in a living human just by looking at these exosomes.
“This study will do this very fancy exosome testing, looking at the information that occurs not just at baseline, but also to see if it’s persisting years later, and what kind of inflammation that is.”
Treatments
The main goal of this study is to identify which inflammatory biomarkers cause worse outcomes in the hopes of targeting treatments to improve patient outcomes.
This includes prevention of long-term degeneration in the brain.
Some of these biomarkers might have preexisting treatments which are available for testing in patients.
On potential treatment, Woo says: “CAPSTONE is critically important in helping us break down inflammation into very specific parts of which cells are doing it, which actual proteins or what we call cytokines are actually causing it, and it looks very deeply into the molecular mechanisms.”
The researchers believe that there will be multiple biomarkers which will be found to cause worse outcomes, so they will prioritise treatments for what is found to have the strongest effects.
However, they hope in the future there will be the potential to personalise treatments based on which group of biomarkers each patient has.
Walsh says that he is excited for the future of ICH treatments: “I’m very excited to see what markers we are able to identify on this larger scale.
“I’m hopeful for the future about the potential of having an actual treatment for ICH based on these inflammatory biomarkers.”
