PDGFR-beta signaling mediates endogenous neurogenesis after postischemic neural stem/progenitor cell transplantation in mice

Abstract

ABSTRACT Objective Although platelet-derived growth factor receptor (PDGFR)-β mediates the self-renewal and multipotency of neural stem/progenitor cells (NSPCs) in vitro and in vivo, its mechanisms of activating endogenous NSPCs following ischemic stroke still remain unproven. Methods The exogenous NSPCs were transplanted into the ischemic striatum of PDGFR-β conditionally neuroepithelial knockout (KO) mice at 24 h after transient middle cerebral artery occlusion (tMCAO). 5-Bromo-2’-deoxyuridine (BrdU) was intraperitoneally injected to label the newly formed endogenous NSPCs. Infarction volume was measured, and behavioral tests were performed. In the subventricular zone (SVZ), proliferation of endogenous NSPCs was tested, and synapse formation and expression of nutritional factors were measured. Results Compared with control mice, KO mice showed larger infarction volume, delayed neurological recovery, reduced numbers of BrdU positive cells, decreased expression of neurogenic factors (including neurofilament, synaptophysin, and brain-derived neurotrophic factor), and decreased synaptic regeneration in SVZ after tMCAO. Moreover, exogenous NSPC transplantation significantly alleviated neurologic dysfunction, promoted neurogenesis, increased expression of neurologic factors, and diminished synaptic deformation in SVZ of FL mice after tMCAO but had no beneficial effect in KO mice. Conclusion PDGFR-β signaling may promote activation of endogenous NSPCs after postischemic NSPC transplantation, and thus represents a novel potential regeneration-based therapeutic target.