Ginseng-Angelica-Sansheng-Pulvis Boosts Neurogenesis Against Focal Cerebral Ischemia-Induced Neurological Deficiency

摘要

Background: The traditional Chinese medicine Ginsing-Angelica-Shanseng-Pulvis (GASP) has been used to treat stroke for 300 years. This present study investigated if it can induce increases in neurogenesis following cerebral ischemic injury. Methods: Rats following middle cerebral artery occlusion were orally treated with high, medium and low doses of a standardized GASP extract. Results: After 14 days, treatment with GASP improved regional blood flow and infarction volume by Magnetic Resonance Imaging scanning, enhanced Ki67+ expression in subventricular zone, increased brain-derived neurotrophic factor (BDNF) secretion, Nestin and bone morphogenetic protein (BMP) 2/4 expressions in hippocampus in a dose dependent manner. Interestingly, low dose treatment with GASP down-regulated doublecortin and Notch1 expressions in hippocampus, as well as up-regulated glial fibrillary acidic protein expression in subgranular zone and hairy and enhancer of split (Hes) 5 expression in hippocampus, while treatment with middle and high doses of GASP reversed these results. Meanwhile, the consumed time was shortened in Basket testandAdhesive removal test and the spending time on exploring novel objects was prolonged by GASP treatment whose effects were more obvious at day 14 post-ischemia. Conclusion: Our study demonstrates that treatment with GASP increases neurogenesis and ameliorates sensorimotor functions and recognition memory. We hypothesis that these effects are thought be mediated by an effect on the BMP2/4 pathway and Notch1/Hes5 signal. Due to its beneficial efficacy, GASP can be recognized as an alternative therapeutic agent for ischemic stroke.