Effect Of Icariin On Learning And Memory Deficits And Angiogenesis In Chronic Cerebral Hypoperfusion Rats

Objective: The current study was designed to explore the effect of icariin(ICA) on learning and memory deficits and angiogenesis in rat induced by chronic cerebral hypo-perfusion.Methods: Vascular dementia(VD) model was established by permanent bilateral occlusion of common carotid arteries(BCCAO), while sham rats only underwent the surgery but not occlusion. Rats were administrated with different doses of ICA(15, 30 and 60 mg/kg) and simvastatin(20 mg/kg) from the 10 th day after surgery, and continued for 2 weeks or 4 weeks. Rats in sham and BCCAO groups were given volume-matched distilled water. Morris water maze was used to test learning and memory function from 9th and 23 th day since treatment; Nissl staining was used to observe neuronal morphology and the number of nissl bodies was counted; immunofluorescence staining with CD31 antibody was used to label microvessels; the content of NO in brain was tested by Griess reagent kits; the protein expression of vascular endothelial growth factor A(VEGFA), vascular endothelial growth factor receptor 2(VEGFR2), matrix metalloproteinase 9(MMP9), brain-derived neurotropic factor(BDNF) and its receptor(Trk B), as well as the level of phosphorylation of extracellular-signal-regulated kinases 1 and 2(ERK1/2), protein kinase B(PKB/Akt), c AMP-response element binding protein(CREB) and endothelial nitric oxide synthase(e NOS) were assayed by Western blot, respectively.Results: Rats administrated with different doses of ICA and simvastatin for 2 weeks or 4 weeks, displayed significantly shorter escape latency of space navigation test, as well as longer time in target region of spatial exploring test compared with BCCAO rats; meanwhile the number of normal neurons and nissl bodies was increased in hippocampus; the density of microvessels labeled by CD31 was increased in cerebral cortex; NO level in cerebral cortex was significantly higher; further, the protein expression of VEGFA, VEGFR2, MMP9, BDNF and Trk B was increased both in cortex and hippocampus, the phosphorylation of ERK1/2, Akt, CREB and e NOS protein was elevated in cortex and hippocampus.Conclusion: Icariin improves learning and memory deficits of BCCAO rats through promoting angiogenesis and directly protecting neuron in brain. The potential mechanisms may be relative to VEGF/VEGFR2 and BDNF/Trk B/CREB signaling pathways in brain.