Introduction: While initial neuronal injury in ischemic stroke stems from the lack of oxygen and nutrients to the brain, subsequent inflammation following reperfusion exacerbates morbidity and mortality. One particular cell that has been previously studied but often overlooked is the mast cell. Better known for their role in allergic diseases, mast cells have more recently been identified as primary immune responders in several modes of neuronal injury. More specifically, murine Mrgprb2 and human MRGPRX2, members of the Mas-related family of G-protein-coupled receptors (Mrgprs), are mast cell-specific G protein-coupled receptors that can be activated by neuropeptides released from injured nerve tissue. Here, we demonstrate that Mrgprb2 is a key receptor necessary for mast cell activation after ischemic stroke in mice.
Methods: Using the middle cerebral artery occlusion model (MCAO), we created a transient ischemic stroke in wild type (WT) mice and Mrgprb2-/- (Knock out) mice. We then looked at the infarct volume for both genotypes using magnetic resonance imaging (MRI). We also quantified neuroinflammation after stroke by performing brain flow cytometry.
Results: We showed that Mrgprb2-/- mice had a 22% ( 5%) reduction in stroke volume as compared to WT mice on edema-adjusted MRI. Mrgprb2-/- also experienced less midline shift following MCAO, consistent with less edema and parenchymal injury. We also showed that Mrgprb2-/- mice exhibit decreased innate inflammation measured by absolute counts of neutrophils, monocytes, and microglia in the stroke hemisphere 48 hours after stroke.
Conclusion : Mrgprb2 contributes to post ischemic stroke injury by amplifying neuroinflammation. Inhibiting this receptor could represent a potential therapeutic approach for ischemic stroke.
.jpg)
