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

Bowen Liu,Chienchih Ke,Xiang Cao,Yonghua Zhao,Yang Li,Cheng Luo,Xiaowei Guan,Yun Xu,Zhenyan Xia,Qian Zhang

doi:10.3389/fnins.2019.00515

Abstract

BackgroundThe traditional Chinese medicine Ginseng-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.MethodsRats following middle cerebral artery occlusion were orally treated with high, medium, and low doses of a standardized GASP extract.ResultsAfter 14 days, treatment with GASP improved regional blood flow and infarction volume by magnetic resonance imaging scanning, enhanced Ki67+ expression in the subventricular zone, increased brain-derived neurotrophic factor (BDNF) secretion, Nestin, and bone morphogenetic protein (BMP) 2/4 expressions in the hippocampus in a dose-dependent manner. Interestingly, low-dose treatment with GASP downregulated doublecortin and Notch1 expressions in the hippocampus, as well as upregulated glial fibrillary acidic protein expression in the subgranular zone and hairy and enhancer of split (Hes) 5 expression in the hippocampus, while treatment with middle and high doses of GASP reversed these results. Meanwhile, the consumed time was shortened in the basket test and the adhesive 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.ConclusionOur study demonstrates that treatment with GASP increases neurogenesis and ameliorates sensorimotor functions and recognition memory. We hypothesize 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.

Highlights

Cerebrovascular disease seriously threatens human life and health, especially in middle-aged and elderly people
Two “reservoirs” of endogenous stem cells have been found in the brain: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, which is important for learning and memory in the brain
We investigate the efficacy and mechanism of GASP on neurogenesis and hypothesize that BMP2 and 4 and Notch1/Hes5 signal pathways are involved in the procedure of neurogenesis after ischemic stroke

Summary

Introduction

Cerebrovascular disease seriously threatens human life and health, especially in middle-aged and elderly people. Proliferated cells in the SVZ directly migrate toward the infarction zone and differentiate and integrate with cerebral parenchyma in adult rodents after stroke (Thored et al, 2006; Yamashita et al, 2006), and the stress of middle cerebral artery occlusion (MCAo) stimulates the proliferation of neuronal progenitor cells in the SGZ (Yagita et al, 2001). These studies have demonstrated that maximizing the efficacy of the brain’s endogenous mechanisms of self-repair is a promising treatment approach. This present study investigated if it can induce increases in neurogenesis following cerebral ischemic injury

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