Tissues and organs generate angiogenesis under the stimulation of angiogenic factors in physiological or pathological conditions.Multiple signal pathways including VEGF, Notch, Wnt/β-catenin, Ang1(2)/tie2 and PIK-Akt etc.have effects on various stages of angiogenesis.VEGF exerts irreplaceable effects on the whole process of angiogenesis through multiple signal pathways.Over the past few years, new progress has been made in the researches of mechanisms regulating angiogenesis through VEGF-related signal pathways both at home and abroad.These findings provide us new theoretical basis for clarification of the pathogenesis of many diseases and clinical drug development.In this article we will summarize the recent research progress in this field, hoping to provide new possibilities for the treatment of angiogenesis-related diseases.

Objective To study the effects of morroniside on the expression of Wnt signaling-related transcription factors neurogenin 2 (Ngn2), Pax6 and Tbr2 in the ischemic ipsilateral cortex 7 days after cerebral ischemia-reperfusion in rats. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of Ngn2, Pax6 and Tbr2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ngn2 increased in the ischemia group compared with the sham group (P<0.05), and it further increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference between the ischemia group and sham group in the expression of Pax6, while it increased the morroniside groups of medium and high dosage compared with the ischemia group (P<0.01). There was no significant difference among all the groups in the expression of Tbr2. Conclusion Morroniside could increase the expression of Ngn2 and Pax6 in the ischemic ipsilateral cortex 7 days after ischemia-reperfusion in rats, suggesting promoting the neurogenesis after ischemia.

Objective To study the effects of morroniside on the expression of matrix metalloproteinase (MMP) -2 and MMP-9 in the peri- infarct cortex 3 days after cerebral ischemia- reperfusion. Methods 15 male Sprague-Dawley rats were randomly divided into sham group (n=3), ischemia group (n=3), and morroniside groups (low, medium and high dosage groups, n=3). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg 3 hours after operation. The expression of MMP-2 and MMP-9 in peri-infarct cortex were detected with immunohistochemistry staining 3 days after operation. Results The expression of MMP-2 and MMP-9 increased in the ischemia group compared with the sham group (P<0.01), and it decreased in all the morroniside groups compared with the ischemia group (P<0.01). Conclusion Morroniside could decrease the expression of MMP-2 and MMP-9 in the peri-infarct cortex 3 days after ischemia, suggesting protecting the function of blood-brain barrier from ischemia.

Aim To observe the change of NF-?B and expression of Bax and Bcl-2 related to apoptosis regulation in the cerebral infarction rat and study the protective effect of iridoid glycoside(IG) extracted from cornus officinalis on focal cerebral ischemia injury and its mechanism of action.Methods Rats were pretreated with drugs by mouth for 7 d and a focal cerebral infarction model of rat was induced by photochemical reaction.Immunohistochemistry and western blot were used to detect the change of expression of NF-?B,Bax and Bcl-2 in the cortex.Results Compared with control group,expression of NF-?B and Bax were increased while expression of Bcl-2 was decreased.Compared with model group,IG(IG 20、60、180 mg?kg~(-1)) markedly decreased the expression of NF-?B and Bax and increased expression of Bcl-2.Conclusion IG has therapeutical effect on cerebral infarction through regulating the expression of NF-?B and apoptosis related genes

AIM: To observe the expression of apoptosis-related proteins in hippocampal neurons of (ovariectomized) (OVX) rats and explore the neuroprotective mechanism of the App17-mer peptide. METHODS: Female Wistar rats were randomly divided into three groups. Bilaterally ovariectomized rats with injection of App 17P peptide (3.5 ?g in 0.1 mL/per rat, three times a week) formed the experimental group (17P+ OVX group). Anti-AIF, Bcl-2 and Bax antibodies were applied in the immunohistochemistry experiment. TUNEL was employed to detect apoptosis. RESULTS: The number of apoptotic neurons was clearly higher in hippocampal and cortex in OVX group than that in OVX+17P group. Immunohistochemistry demonstrated the increased expression of AIF, Bax in hippocampal neurons of OVX group. OVX group showed a significantly reduced expression of Bcl-2 in hippocampal neurons. Hippocampal tissue from OVX group showed the increased expression of AIF, Bax, and showed diminished expression of Bcl-2, treating with App17-mer peptide normalized the expression of these proteins. CONCLUSIONS: The expression of apoptosis-related proteins were abnormal in the OVX rats, App17-mer peptide normalized these changes. Estrogen deficiency induced neuronal apoptosis, and App17-mer peptide diminished apoptosis.

Objective To investigate the effects of Morroniside on H2O2-induced oxidative injury in SH-SY5Y neuroblastoma cells.MethodsSH-SY5Y cells were pre-incubated with Morroniside(1,10,and 100 μmol/L)for 24 h prior to exposure to H2O2(500 μmol/L)for 18 h.The content of reactive oxygen species(ROS),nitric oxide(NO),glutathione(GSH)were determined.ResultsPretreatment the cells with Morroniside(10 and 100 μmol/L)lowered H2O2-induced ROS release by 37%(P<0.01)and 27%(P<0.05)versus H2O2,and NO release in a dose-dependent manner by 31%(P<0.05),53%(P<0.01)versus H2O2.Morroniside(1,10,and 100 μmol/L)increased GSH level in cells treated with H2O2 in comparison with cells exposed only to H2O2,respectively.ConclusionMorroniside shows neuroprotection effect against H2O2-induced oxidation injury in SH-SY5Y cell.

ObjectiveTo explore the mechanism of protection of 2,3,5,4'-tetrahydroxy stilbene-2-O-β-D-glucoside(TSG) on brain.MethodsThe bilateral carotid arteries of mice were occluded and then reperfused. The mice were sacrificed to get the brain tissue. Brain water content(BWC) was assayed by dry-wet method; malondialdehyde (MDA) content was determined by thiobarbiturate method and the activity of superoxide dismutase(SOD) was estimated by nitrite salt assay.ResultsBWC of model group was significantly higher than that of sham-operation group, while the TSG treatment reduced the BWC remarkably in mice with ischemia-reperfusion. SOD activity of model group was significantly lower than that of sham-operation group, while MDA content increased remarkably. Comparing with the model group, the SOD activity of mice treated with TSG was higher and the MDA content was lower.ConclusionTSG may reduce brain edema, improve the anti-oxidative ability of the brain tissue, and therefore, have protective effects on the brain.

Neural stem cells are a category of cells with self-renewal and differentiation potential. Proliferation and differentiation of neural stem cells have closely relation with growth factor, cell factor, environmental signal, and so on. In recent years, evidence indicates that neural stem cells possessing multipotency naturally occur in adult brain. The found of adult neural stem cells have changed the theory that central nervous system cannot regenerative. Chinese Traditional Medicine can effectively induce adult neural stem cells to proliferate and differentiate, opening up unprecedented direction in the research for the treatment of nerve regeneration, and showing great potency for curing cerebral ischemic injury.

Objective To explore the effects of morroniside on the expression of Angiopoietin-1 (Ang-1) and Tie-2 in a rat after focal cerebral ischemia-reperfusion. Methods 20 male Sprague-Dawley rats were randomly divided into sham group (n=4), ischemia group (n=4), and morroniside groups (low, medium and high dosage groups, n=4). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg after operation. The expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ang-1 and Tie-2 increased in the ischemia group compared with the sham group (P<0.01), and both of them further increased in the morroniside groups of high dosage compared with the ischemia group (P<0.01), and the expression of Tie-2 also increased in the morroniside groups of medium dosage (P<0.001). Conclusion Morroniside could increase the expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, suggesting promoting the angiogenesis after ischemia.

There is a close relationship between the Wnt signaling and neurogenesis/angiogenesis, which is significant in the regulation of the brain plasticity. Investigations on the mechanism of Wnt signaling in neurogenesis and angiogenesis are under way, and these investigations contribute to the recognition of the restoration and regeneration after the brain injury.