Recognition, Intervention, and Monitoring of Neutrophils in Acute Ischemic Stroke

Abstract

Neutrophils are implicated in numerous inflammatory diseases, and especially in acute ischemic stroke (AIS). The unchecked migration of neutrophils into cerebral ischemic regions, and their subsequent release of reactive oxygen species, are considered the primary causes of reperfusion injury following AIS. Reducing the infiltration of inflammatory neutrophils may therefore be a useful therapy for AIS. Here, inspired by the specific cell–cell recognition that occurs between platelets and inflammatory neutrophils, we describe platelet-mimetic nanoparticles (PTNPs) that can be used to directly recognize, intervene, and monitor inflammatory neutrophils in the AIS treatment and therapeutic evaluation. We demonstrate that PTNPs, coloaded with piceatannol, a selective spleen tyrosine kinase inhibitor, and superparamagnetic iron oxide (SPIO), a T2 contrast agent, can successfully recognize adherent neutrophils via platelet membrane coating. The loaded piceatannol could then be delivered to adherent neutrophils and detach them into circulation, thus decreasing neutrophil infiltration and reducing infarct size. Moreover, when coupled with magnetic resonance imaging, internalized SPIO could be used to monitor the inflammatory neutrophils, associated with therapeutic effects, in real time. This approach is an innovative method for both the treatment and therapeutic evaluation of AIS, and provides new insights into how to treat and monitor neutrophil-associated diseases.

High Neutrophil-to-Platelet Ratio Is Associated With Hemorrhagic Transformation in Patients With Acute Ischemic Stroke

“…The interaction between neutrophil and platelet was involved in the process of vascular injury after ischemic stroke (16). Platelet could facilitate neutrophil recruitment and extravasation into brain parenchyma after stroke, and the amount of infiltrated neutrophil was correlated with stroke progression (17,18). Moreover, high neutrophil-platelet complex formation may increase the risk of stroke in patients with symptomatic carotid stenosis (19).…”

Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?

“…Piceatannol is a selective tyrosine kinase inhibitor. Like the CXCL1-soaked sponge, piceatannol, a selective tyrosine kinase inhibitor, can successfully recognize, intervene, monitor, and detach neutrophils into circulation, limiting infiltration of neutrophils in ischemia ( 220 ). Small extracellular vesicles derived from mesenchymal stromal cells protected against BBB disruption, ischemic injury, and neurological dysfunction, specifically by modulating the entry and accumulation of neutrophils ( 221 ).…”

Recent Advances of Cell Membrane Coated Nanoparticles in Treating Cardiovascular Disorders

“…Studies have shown potential curative benefits through alleviating the infiltration of neutrophils [ 102 ]. Inspired by these findings, Tang et al innovatively constructed a platelet membrane coated PLGA nanoplatform with superparamagnetic iron oxide nanoparticles and piceatannol loaded (PTNPs) ( Figure 4 A) [ 103 ]. In their study, the coated platelet membranes facilitated binding between nanoparticles and neutrophils through the recognition of P-selectin (platelet) and PSGL-1 (neutrophil).…”