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This study aimed to illustrate the mechanism by which Shenmayizhi decoction (SMYZD) improves the learning memory of rats with vascular cognitive impairment (VCI). Fifty male and female Wistar rats of specific pathogen-free grade (SPF grade) were used to establish the model by the administration of a microsphere embolization. This was accomplished by injecting sterile, standardized, mass-produced microspheres of uniform particle size (100–200 µm in diameter) in a sodium alginate microsphere vascular embolic agent suspension to induce VCI. The VCI model was successfully established in 40 rats, including both male and female rats, and the rats were randomly divided into 4 groups of 10 rats each. The model group was administered an equal volume of distilled water. The donepezil group was administered 0.45 mg/kg/d donepezil, which is equivalent to the clinical dosage. The SMYZ-H group was administered 11.88 g/kg/d SMYZ, which is 4 times higher than the clinically equivalent dosage. The SMYZ-L group was administered 2.97 g/kg/d SMYZ, which is the clinically equivalent dosage. A sham-operated group was used as the control group and administered an equal volume of distilled water. The rats in the 4 groups were treated by gavage with equal volumes of liquid and the indicated concentration of drug diluted in distilled water for 8 consecutive weeks. Two months later, the Morris water maze (MWM) was used to evaluate the spatial memory of all the rats. Ultrastructural and ultrapathological changes in the capillaries of the cerebral cortex were observed by transmission electron microscopy. Furthermore, Western blot and RT-PCR analyses were used to assess the levels of platelet-derived growth factor receptor-β (PDGFR-β), neuron-glial antigen 2 (NG2), vascular endothelial growth factor A (VEGF-A), and angiopoietin 1 (Ang1) in the cerebral cortex of the rats. The results showed that SMYZD at concentrations of 11.88 g/kg/d and 2.97 g/kg/d (SMYZ-H and SMYZ-L) significantly shortened the escape latency (EL). In addition, SMYZ-H significantly prolonged the distance traveled and the time spent in the original platform quadrant by the rats with VCI. SMYZ-H significantly increased the NG2 and Ang1 protein expression levels and increased the PDGFR-β and Ang1 mRNA levels. These results demonstrated that Shenmayizhi decoction can improve the memory abilities of rats with VCI induced by multiple cerebral infarctions by preventing pericyte degeneration. [ABSTRACT FROM AUTHOR]