Synergistic effect of tanshinone IIA and mesenchymal stem cells on preventing learning and memory deficits via anti-apoptosis, attenuating tau phosphorylation and enhancing the activity of central cholinergic system in vascular dementia.

Vascular dementia (VaD) is one of common causes of dementia following Alzheimer's disease. However, up to date, there has been no effective treatment for VaD yet. Cellular therapy with mesenchymal stem cells (MSCs) and some extract ingredients of traditional Chinese medicines are expected to improve learning and memory function in VaD model. In this study, we applied tanshinone II A (TSA) and MSCs in the rat model of VaD to evaluate the synergistic effect of TSA and MSCs on preventing cognitive deficits as well as explore the underlying mechanism. The VaD model was established by using modified four-vessel occlusion(4-VO) on rats. Our results showed that TSA combined with MSCs treatment provided a better protecting effect on spatial learning and memory function in the VaD rats than those treated with either MSCs or TSA only. The combined administration of TSA and MSCs demonstrated a synergistic effect on suppressing neuronal apoptosis in the hippocampus, attenuating tau phosphorylation and enhancing the activity of central cholinergic system. These results indicated that the combination of TSA and MSCs exhibits better therapeutic effects on learning and memory protection than the treatment with either MSCs or TSA only, suggesting a potential novel treatment for VaD.