International Business Department           Liu Bojia           July 29, 2024

  Ischaemic stroke, also known as stroke, is an acute brain injury that is a significant contributor to death and long-term disability in adults. In addition to damaging the brain and its functions, stroke also affects other organs in the body, such as the heart, often leading to complications such as arrhythmia and myocardial infarction, and stroke-related cardiac dysfunction can occur even in patients who did not have heart disease prior to the stroke.

  Professor Arthur Liesz of the Institute for Stroke and Dementia Research at the University Hospital of Munich, Germany, has conducted research into the effects of brain injury on the heart in the hope of finding effective ways to prevent secondary heart disease after stroke. In a recent paper published in the leading academic journal Cell, the team revealed that changes in a group of immune cells are key mediators of the cardiac dysfunction caused by ischaemic stroke, and that immune-targeted therapies could therefore serve as a potential preventive approach.

  Specifically, through single-cell sequencing, the researchers found that after a period of time after inflicting ischaemic acute brain injury to experimental mice, even after their nervous system had mostly returned to normal, the innate immune cells (monocytes, macrophages) in their bloodstreams and in several organs continued to show a distinct pro-inflammatory phenotype, with persistent changes in their gene expression profiles, which were epigenetically reprogrammed to form the innate immune memory.

  Intriguingly, this persistent inflammatory change in the monocyte/macrophage population is particularly evident in the heart. Following the occurrence of a stroke, monocytes in the blood are recruited to the heart where they differentiate into macrophages that reside in the heart tissue. Experimental results have demonstrated that this leads to cardiac fibrosis, which impairs the heart's pumping function.

  Based on these observations, the researchers envisioned strategies to counteract them: blocking innate immune cells from forming memories through epigenetic reprogramming, and blocking pro-inflammatory monocytes from running into the heart. For the former, this could be achieved by blocking IL-1β with antibodies, as they found that this pro-inflammatory cytokine is a key driver of the innate immune memory formation that is affected after a stroke, while for the latter, a dual chemokine CCR2/5 inhibitor could be used to limit the movement of monocytes.

  In the paper, this strategy has been validated in a mouse model for the prevention of post-stroke cardiac insufficiency.Professor Liesz noted that the results of this new study on heart-brain interactions could provide a new guiding framework for secondary prevention immunotherapy in stroke.