Restorative effect of modified dioscorea pills on the structure of hippocampal neurovascular unit in an animal model of chronic cerebral hypoperfusion

Abstract

Introduction A considerable part of old people suffer from Chronic Cerebral Hypoperfusion (CCH) in their long lives but have no way to change. The Modified Dioscorea Pills (MDP), a Chinese compound herbal prescription, has good clinical efficacy for CCH related diseases such as Vascular Dementia, whereas, what happened and how MDP works in CCH need to be clarified. Here, we investigate the neural inflammation and gliosis, neuronal apoptosis and regeneration in an animal model of CCH and interfered with MDP to explore some mechanisms of this Chinese herbal medication. Methods 40 rats were randomly divided into Sham operated Group, Model Group and MDP Group according to a Random Number Table. CCH models were made by the modified 2-VO (two vessels occlusion) operation. The intelligence of rats were measured by Morris Water Maze (MWM) test; H & E staining and transmission electron microscope (TEM) were applied to observe the pathological and ultrastructural changes in hippocampus; The expression of key genes including growth associated protein 43 (GAP-43) and vascular endothelial growth factor (VEGF) and key protein including Bax, Bcl-2, nuclear factor-κB (NF-κB p65), microtubule associated protein-2 (MAP-2), Oligodendrocyte transcription factor 2(Olig-2), glial fibrillary acidic protein (GFAP) of hippocampus were detected. Results CCH lead to learning and memorial impairment and MDP can partly restore them; Neural inflammation, Neuronal apoptosis and astrocyte hyperplasia were common in Model Group but they were partly reversed by MDP; The expressions of GAP-43mRAN and VEGF mRNA in Model Group were much higher than those in Sham operated Group, but they reached the highest in MDP Group (P < 0.01 or P < 0.05). Conclusions Through regulating the expressions of key genes and proteins, MDP partly restore the intrinsic structure of Neurovascular Unit (NVU) in hippocampus, which revealed one of its therapeutic mechanisms on CCH.