Stroke is now the second leading cause of death worldwide. Spontaneous intracerebral hemorrhage (ICH) is the deadliest type of stroke, killing 50% of its victims within one month. If we can understand how ICH damages brain tissue, we will be better equipped to develop new prognostic and therapeutic tools.
ICH occurs when a blood vessel ruptures and bleeds into the brain. As blood pools, it compresses the surrounding tissue and breaks down into toxic products, resulting in cell death and brain damage. This initial injury triggers harmful secondary “cascades” like swelling and inflammation, initiating a vicious cycle of tissue damage that can persist for days or weeks after injury.
Despite extensive studies, effective medical and surgical treatments for ICH remain limited. One key factor in ICH treatment is the identification of patients at high risk for poor outcomes. As ICH is a medical emergency, new strategies for early diagnosis and sensitive prediction of ICH outcome are critically needed. The ideal predictive tool, often called a “biomarker”, should be simple, fast and cost-effective. Importantly, ICH patients commonly receive blood draws as part of their care, making blood-based biomarkers highly accessible and cost-effective.
CD163 is a receptor found on many cells, including brain-resident immune microglia and circulating immune cells. When these cells encounter blood or dangerous blood products, this receptor allows them to bind and remove the toxic substances. CD163 levels increase in the brain after ICH, but measurement of brain CD163 is not a practical biomarker. Interestingly, CD163 can be cut from the cell surface, creating a soluble form (sCD163) that circulates throughout the body. We then asked: Is sCD163 a useful blood-based biomarker in ICH patients?
The aim of our current research is to understand the relationship between levels of sCD163 and ICH outcome. We believed that blood sCD163 might be a valuable tool for identifying patients at greater risk of complications and poor outcome, who may benefit from more aggressive treatment.
Using blood samples from ICH patients, we found that sCD163 increased early after ICH and continued to rise over time, indicating the potential value of sCD163 as a pre-hospital diagnostic test. We also found that sCD163 in the cerebrospinal fluid (CSF) increases after ICH, and that the vast majority of CSF sCD163 was generated in the brain itself. As predicted, low levels of sCD163 early after ICH indicated that patients would go on to develop delayed bleeding and perihematomal swelling in the brain, two significant and potentially deadly complications of ICH. Our results suggest that sCD163 may be useful in the clinic as an indicator of inflammation and predictor of poor outcome in ICH patients.
Interestingly, sCD163 is thought to retain its anti-inflammatory abilities after being shed from the cell surface. Future studies will focus on determining the biological role of sCD163 after ICH, as sCD163 supplementation in high-risk patients may prove to be a novel and powerful therapeutic strategy for the prevention of death and disability in millions of ICH patients worldwide.
This study, Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema was recently published in the journal Annals of Clinical and Translational Neurology.