Abstract: The aim of this study was to investigate the protective effect and mechanism of Ganoderma leucocontextum (GLAE) aqueous extracts on hippocampal neurons after cerebral ischemia. Fifty rats were divided into control, model, low-(0.05 mg/(g·BW)), middle-(0.1 mg/(g·BW)) and high-dose (0.2 mg/(g·BW)) GLAE groups. The cerebral ischemia model of rats was established by bilateral common carotid artery occlusion, and then treated intragastrically with different doses of GLAE once a day for two weeks, and rats of control and model groups were administered the same volume of normal saline. Step down test was used to assess memory acquisition, memory consodilidation and memory reappearance disorder in rats learning and memory ability. The rats pathological changes in hippocampus were observed by HE staining. The nitric oxide synthase(NOS) activity and nitric oxide (NO) content were determined by colorimetric method. The levels of growth associated protein-43 (GAP-43) and brain derived neurotrophic factor (BDNF) in hippocampus were detected by Western blotting and Real-time quantitative PCR, respectively. The results showed that when compared to control group, in the model group, the escape latency of rats in step down test were significantly shortened and the number of electric shocks were significantly increased (P<0.05), hippocampal neurons exhibited obviously degenerative changes with pyknosis and a loose and disorderly arrangement, and a decrease in cell number (P<0.05), NOS activity and NO content were significantly decreased (P<0.05), the level of GAP-43 protein of hippocampal tissue was significantly increased (P<0.05), BDNF mRNA level of hippocampal tissue was significantly decreased (P<0.05). When compared to model group, GLAE administration could obviously prolong the escape latency of rats and decrease significantly the number of electric shocks (P<0.05), the morphology of neurons in GLAE high-dose group of CA1 area and dentate gyrus was significantly improved, and the number of neurons was significantly increased (P<0.05), GLAE low-dose group had no significant effect on NOS activity (P>0.05), but significantly increased the content of NO (P<0.05), while the activity of NOS and the content of NO were significantly increased in middle- and high-dose groups of GLAE (P<0.05). The expression of GAP-43 protein in hippocampus of GLAE low-, middle- and high-dose groups were significantly increased (P<0.05), the level of BDNF mRNA of GLAE low-, middle- and high-dose groups were significantly increased (P<0.05). The above results indicated that GLAE had a certain protective effect on hippocampal neurons injury after cerebral ischemia by increasing the activity of NOS and the content of NO, promoting the hippocampal neurogenesis and neuro-functional recovery, and could improve cognitive function of rats. The effect of 0.2 mg/g GLAE was the best.

Key words: Ganoderma leucocontextum aqueous extracts; cerebral ischemia; rats; nitric oxide synthase (NOS); growth associated protein-43(GAP-43); brain derived neurotrophic factor(BDNF)