Inhibition of Salvianolic Acid B and Ginsenoside Rg1 on Hemorrhagic Transformation after Stroke

Abstract Objective  Application of recanalization on stroke patients is not only limited with time window, but also accompanied with the risk of hemorrhagic transformation. In present study, the effects of salvianolic acid B and ginsenoside Rg1 combination (SalB/Rg1) on time window and hemorrhagic transformation against ischemic stroke was evaluated on middle cerebral artery occlusion (MCAO) mice. Methods  The protection and time window of SalB/Rg1 were estimated through infarct volume, neurobehavioral deficits, and histomorphological examination. The prohibition of SalB/Rg1 against hemorrhagic transformation was detected on MCAO mice stimulated with dextrose and reperfusion. Hemorrhagic transformation was assessed by the Heidelberg Bleeding Classification. The mechanism of SalB/Rg1 against hemorrhagic transformation was identified by immunofluorescence staining and in situ gelatin zymography. Results  First, SalB/Rg1 significantly reduced infarct volume and improved neurobehavior in a dose-dependent manner. Then, the protective time window up to 9 hours was detected for SalB/Rg1 against stroke. Both the dose-dependent efficiency and longtime protection of SalB/Rg1 were further identified based on cytoarchitecture through histopathological stain. Second, SalB/Rg1 downregulated hemorrhagic score, infarct volume, and abnormal neurobehavior. Finally, the inhibition of SalB/Rg1 against hemorrhagic transformation was found to accompany with its protection on the integrity of neurovascular unit. Around the edge area of infarction, SalB/Rg1 attenuated the astrocyte activation, maintained the abundance of junction protein (claudin-5) between endothelial cells, considerably decreased matrix metallopeptidase 9 activity through in situ gelatin zymography. Conclusion  SalB/Rg1 is a promising strategy for further development against stroke, especially against hemorrhagic transformation.