Radix Angelica Sinensis Promotes Adult Neurogenesis To Mediate Recovery From Vascular Cognitive Impairment

Objective Radix Angelica Sinensis (RAS) has beneficial effects in patients suffering from cognitive impairment associated with chronic cerebral hypoperfusion. Neurogenesis, which is a lifelong process, is thought to be important for cognitive function. Here, we studied the effects of RAS on cognitive improvement and neurogenic enhancement and examined the possible underlying mechanisms in a rat model with permanent bilateral common carotid artery occlusion (2VO), which serves as a model of chronic cerebral hypoperfusion-related neurodegenerative diseases.Methods The rats were randomly divided into the following five groups:sham-operated rats treated with sterile water (Sham group),2VO rats treated with sterile water (2VO group),2VO rats treated with sterile water and received cranial irradiation (2V0+IRR group),2VO rats treated with1g/kg of RAS per day (2VO+RAS group) and, finally,2VO rats treated with1g/kg of RAS per day and received cranial irradiation (2VO+IRR+RAS group). Spatial learning and memory were measured using a Morris water maze.5-bromo-2'-deoxyuridine(BrdU) and BrdU/neuronal nuclei (NeuN) immunohistological staining was performed to investigate the impact of RAS on the proliferation and survival of adult-born neurons. Immunohistological analyses of glutamic acid decarboxylase65(GAD65) and presynaptic vesicular glutamate transporter1(VGLUT1) were performed as well. Western blot was used to analyse brain-derived neurotrophic factor (BDNF), phosphorylated cAMP-responsive element binding protein (p-CREB) and cognition-related molecules-synaptophysin(SYN) and postsynaptic density protein-95(PSD-95).Results RAS enhances adult neurogenesis in the hippocampus following chronic cerebral hypoperfusion and improves the cognitive decline associated with hypoperfusion. Long-term ablation of adult hippocampal neurogenesis through cranial irradiation abolishes the protective effects of RAS on cognition. Furthermore, administration of RAS restores the decrease BDNF expression, p-CREB and GAD65staining intensity in rats suffering from chronic cerebral hypoperfusion.Conclusion The present study supports the hypothesis that adult neurogenesis is required for RAS to facilitate recovery from the cognitive impairment induced by chronic cerebral hypoperfusion, while neurogenic enhancement secondary to the RAS treatment may be due to increased BDNF and p-CREB levels and increasedy-aminobutyric acid (GABA) expression. Based on the possible mechanisms suggested by the present study, this well-known traditional medicine may represent a candidate therapeutic agent for the treatment of dementia associated with vascular injury.