Therapeutic Potential of Platelet-Derived Growth Factor-B-Modified Nanoparticles in Enhancing Pericyte Activation for Acute Ischemic Stroke

Platelet-derived growth factor subunit B (PDGF-B) signaling plays a critical role in pericyte activation and neurovascular repair following ischemic injury. Although enhancing PDGF-B signaling in pericytes represents a promising therapeutic strategy for ischemic stroke, practical approaches have not yet been developed. In this study, we evaluated the therapeutic efficacy and underlying mechanisms of PDGF-B-modified heat shock protein nanoparticles (PDGF-B HSPNPs) in a transient middle cerebral artery occlusion (tMCAO) mouse model of either sex. Mice were treated with single intravenous injection of PDGF-B HSPNPs immediately after reperfusion, and infarct volume and motor function were assessed. To investigate cellular effects, flow cytometric analysis of brain-derived single-cell suspensions was performed three days after treatment to quantify Platelet-derived growth factor receptorβ (PDGFRβ)-positive pericytes. Our results demonstrate that PDGF-B HSPNPs administration significantly reduced infarct volume and improved motor function, accompanied by enhanced activation of pericytes in the peri-infarct region. These findings suggest that PDGF-B HSPNPs represent a promising therapeutic approach for the treatment of ischemic stroke. Significance Statement In this study, we demonstrated that immediate post-reperfusion administration of PDGF-B HSPNPs significanly improved the outcomes including the infarct volume and motor function recovery in a transient MCA occlusion mouse model. Importantly, our data revealed a possible mechanism by which PDGF-B HSPNPs enhance early activation of pericytes and endothelial cells—critical components of the neurovascular unit—leading to reduced infarct size and improved motor function. These findings suggest that nanoparticle-based targeting of pericyte pathways may represents a promising therapeutic strategy for acute ischemic stroke.