The experimental research on neuroplasticity in rats' hippocampus subjected to chronic cerebral hypoperfusion and interfered by Modified Dioscorea Pills

Background: Chronic Cerebral Hypoperfusion (CCH) is a common, crucial and tough problem for old people. It easily leads to Lacunar Infarction and even Vascular Dementia (VD). Western medicine has the advantage to relieve some VD symptoms but fails to cure it. Some classic Chinese medicines have good efficacies to treat and delay the cerebral functional decline resulted from CCH. Among them Modified Dioscorea Pills (MDP) has been proven to have a convincing effect in curing VD. So far the knowledge about neuroplasticity in CCH is little known and the underlying interfered mechanism by MDP on neuroplasticity has not yet been explored. This study explores the changes of neuroplasticity involving neurogenesis, angiogenesis and synaptogenesis in CCH and interfered by MDP.

Methods: 40 male SD rats were divided into the Sham operated Group, the Model Group and the MDP Group according to a Random Number Table. Bilateral Common Carotid Arteries Occlusion (BCCAO) was adopted to prepare CCH models. MDP condense decoction had been administered by gavage to rats in the MDP Group (10g·Kg-1·d-1) for 45 days; Rats in the other two groups were accepted normal salts as substitution with same dosage and course. Through Morris Water Maze (MWM) test, pathological observation of hippocampus, ultrastructural study on synapse, Real Time Polymerase Chain Reaction (RT-PCR) and immunohistochemistry detection, the capacities of intelligence of rats, the morphological character of hippocampus CA1 zone and the synapse associated protein and gene such as Growth Associated Protein (GAP-43) mRNA, Vascular Endothelial Growth Factor (VEGF) mRNA, Microtubule-associated Protein (MAP)-2, Synaptophysin (SYP), Postsynaptic Density protein (PSD)-95 and Micro Vessel Density (MVD) were determined. Through one-way ANOVA the data was analyzed and when P＜0.05 the result was considered significant.

Results: Compared to the Model Group, rats in the MDP Group achieved much better behavioral performance (P＜0.05); more neurons and more synapses regenerated; the expression of SYP, PSD-95and MAP-2 up-regulated (P＜0.05); The expressions of GAP-43 mRNA and VEGF mRNA in the Model Group were higher than those in the Sham operated Group (P＜0.05), but they reached the highest in the MDP Group (P＜0.05); The count of MVD in the Sham operated Group is the lowest, it is higher in the MDP Group and it reaches highest in the Model Group (P＜0.05).

Conclusions: Some key genes promoting neuroplasticity such as GAP-43 mRNA and VEGF mRNA remarkably up-regulated in CCH, they only boost angiogenesis but fail to facilitate neurogenesis and synaptogenesis in CCH. However, accompanied by furtherly up-regulation of these two key genes, MDP obviously improves neurogenesis, synaptogenesis and temperate angiogenesis in CCH which may be underlying its good efficacy.