Targeting Formyl Peptide Receptors to Promote Resolution Following Cerebral Ischaemia/Reperfusion Injury in Sickle Cell Disease
Ischaemic stroke is a leading cause of death and disability, with inflammation crucially involved in AIS pathophysiology. During ischaemic stroke, blood supply to parts of the brain becomes limited causing cell death. This complex response involves blood vessels, chemical mediators and immune cells (termed “inflammation”). Ongoing or worsening inflammation further damages the brain. Reducing, and ideally eliminating inflammation is critical to recovery from stroke – a process termed ‘resolution’. The ideal outcome of inflammation is its resolution, which is a tightly orchestrated process. We are particularly interested in one key player of resolution, the formyl peptide receptor 2 (Fpr2/ALX), which is found on certain immune cells. In mice, targeting Fpr2/ALX limits brain damage during stroke.
This project focuses on an in vivo model of stroke that is coupled to a chronic inflammatory condition: Sickle Cell Disease (SCD), a disorder affecting red blood cells. People with SCD have chronic inflammation throughout their bodies and are at high-risk of ischaemic stroke. We are investigating whether targeting the Fpr2/ALX, which resolves inflammation, can limit brain damage during SCD-associated stroke.
The Gavins laboratory acknowledges the urgent unmet clinical need to uncover novel strategies to ameliorate post-stroke inflammation, especially among individuals with SCD. Our focus extends beyond mere inflammation mitigation; we aim to restore cerebral homeostasis while safeguarding neuronal integrity and preserving the integrity of the blood-brain barrier. Employing cutting-edge methodologies and advanced technologies, our endeavour is to facilitate inflammation resolution and enhance outcomes.