Neuroimmunology of stroke

Stroke is a major cause of mortality and morbidity with injury-modifying treatment available to only a small fraction of patients (~5%). Our work is focussed on immune mechanisms that influence stroke-related injury, recovery and complications with the aim of developing novel interventions and biomarkers. We have two major areas of research and opportunities for projects:

1) Stroke-associated infection and systemic immunosuppression. Infection is a common complication affecting patients early after stroke and the leading cause of mortality after the brain injury itself. Mechanisms predisposing to infection are poorly understood and predictive biomarkers are limited. Our recent work has uncovered previously unknown mechanisms that could contribute to stroke-induced infection and related mortality. A key discovery is that a specific B cell population in the spleen essential for early anti-bacterial defence against the pathogens commonly affecting stroke patients is depleted and its function impaired after experimental stroke in mice. Preventing these changes is associated with protection from stroke-induced pneumonia. Preliminary studies have also shown that we can detect this B cell population in healthy human blood and could use this as a surrogate biomarker of splenic B cell function. Ongoing work is investigating the neuroimmune pathways driving these systemic immune cell alterations, establishing the potential utility of B cell biomarkers in patients and testing efficacy of B cell modifying interventions in limiting infection.

2) Resolution of injury-causing inflammation after stroke and promoting brain repair. Inflammation is implicated in multiple phases of stroke pathophysiology and has both harmful and beneficial effects on brain injury and repair. A key goal of immunomodulatory interventions in stroke is therefore to limit or resolve tissue-damaging inflammation without compromising the regeneration-promoting effects of neuroinflammatory activity. We are investigating mediators and mechanisms that could promote a favourable balance of inflammatory activity in the brain after stroke. This includes the role of TREM2, a protein expressed by microglia and other myeloid cells that our recent data suggests can drive resolution of injurious inflammation. We are also studying the involvement of different subpopulations of myeloid cells (microglial, monocytes, macrophages) that may have distinct roles in injury-causing, resolution-regulating and repair-promoting aspects of neuroinflammatory activity after stroke. These studies are largely using experimental models of stroke but future work will explore relevant markers in patient and post-mortem samples.