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OBJECTIVE:To explore the protective mechanisms of the Traditional Chinese Medicine Bushenhuoxue (BSHX) in a rat model of vascular dementia (VD).METHODS:A rat model of VD was developed usingbilateral common carotid artery occlusion (BCCAO).Rats were administered BSHX (10.14 or 5.07 g/kg),nimodipine (11.06 mg/kg;positive control),or saline (control) by gavage daily for 30 d post-surgery.Leing and memory abilities were assessed using the Morris water maze.Morphological changes in the hippocampus were observed using light microscopy (hematoxylin and eosin staining) and transmission electron microscopy (TEM).The mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF),tyrosine receptor kinase B (TrkB),phosphatidyl inositol 3-kinase (PI3K),serine/threonine kinase (AKT),and cAMP response element binding protein (CREB) were measured by real-time polymerase chain reaction (RT-PCR) and West blot,respectively.RESULTS:Compared with the sham group,rats with BCCAO exhibited impaired leing and memory abilities (Morris water maze) and showed abnormalities in neuronal morphology (light microscopy)and ultrastructure (TEM) in the hippocampus.They also had decreased mRNA and protein expressions of BDNF,TrkB,PI3K,AKT,and CREB in hippocampal tissue (all P ＜ 0.05).In rats with BCCAO,administration of BSHX attenuated deficits in leing and memory,improved the morphology and ultrastructure of hippocampal neurons,and enhanced mRNA and protein expression levels of BDNF,TrkB,PI3K,AKT,and CREB (all P ＜ 0.05).CONCLUSION:BSHX may protect hippocampal neurons and improve leing and memory abilities,at least in part via the activation of BDNF/TrkB/PI3K/AKT/CREB signaling.