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. To test this hypothesis, we are initiating stroke in SCD mice to study its extent in the presence of drugs affecting Fpr2/ALX.
The potential impact of this research project is far reaching. It will provide insight into the pathophysiology of stroke, discovering novel ways to promote resolution of inflammation post stroke in SCD.
Reducing inflammation in the brain after stroke
Professor Felicity Gavin's explains her stroke research in The Royal Society video