Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central ...Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair.Ginkgolide B has a robust neuroprotective effect.In this study,we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo.Neural stem cells were treated with 20,40 and 60 mg/L ginkgolide B in vitro.Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase,glial fibrillary acid protein and suppressor of cytokine signaling 2.After treatment with 40 and 60 mg/L ginkgolide B,cells were large,with long processes.Moreover,the proportions of neuron-specific enolase-,glial fibrillary acid protein-and suppressor of cytokine signaling 2-positive cells increased.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.Six hours after ischemia,ginkgolide B(20 mg/kg) was intraperitoneally injected,once a day.Zea Longa's method was used to assess neurological function.Immunohistochemistry was performed to evaluate the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells.Real-time quantitative polymerase chain reaction was used to measure m RNA expression of brain-derived neurotrophic factor and epidermal growth factor.Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2.Ginkgolide B decreased the neurological deficit score,increased the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells,increased the m RNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra.Together,the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury.展开更多
Background:A rapid elevation of post-ischemic circulating hepatocyte growth factor(HGF)levels has been reported in acute vascular disease including stroke.However,the impact of transient ischemic attack(TIA)on circula...Background:A rapid elevation of post-ischemic circulating hepatocyte growth factor(HGF)levels has been reported in acute vascular disease including stroke.However,the impact of transient ischemic attack(TIA)on circulating HGF has never been studied.Methods:Patients with an onset of either stroke or TIA within the past 30 days were enrolled.Based on the ischemic event,the patients were divided into a stroke group and a TIA group.Blood samples were collected at enrollment and at follow-up visits at one,three,and six months until a recurrent cerebral ischemic event.Plasma levels of HGF were measured using an enzyme-linked immunosorbent assay and logarithmically transformed to eliminate skewness.Results:Thirty-six patients were enrolled in the study,with 20 in the stroke group and 16 in the TIA group.The dynamic HGF levels post-ischemia showed distinct patterns between the two groups.A significant decrease of HGF levels was observed in the stroke group,from 2.62±0.18 ng/mL within 30 days after stroke to 2.41±0.22 ng/mL beyond 30 days(P=0.026);however,no significant change was found in the TIA group(2.22±0.17 ng/mL vs.2.19±0.16 ng/mL,P=0.990).A multivariate regression analysis showed a last event of stroke and a comorbidity of systemic atherosclerotic disease(SAD)were independently associated with higher levels of HGF.Subgroup analyses showed HGF levels decreased from 2.64±0.22 ng/mL within 30 days after stroke to 2.36±0.18 ng/mL beyond 30 days in patients without SAD(P=0.008),but not in patients with SAD(P=0.700).Conclusion:Our data indicate that in patients without SAD,circulating HGF is a potential biomarker to distinguish between stroke and TIA.展开更多
基金supported by the National Natural Science Foundation of China,No.81073082 to JSZ
文摘Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair.Ginkgolide B has a robust neuroprotective effect.In this study,we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo.Neural stem cells were treated with 20,40 and 60 mg/L ginkgolide B in vitro.Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase,glial fibrillary acid protein and suppressor of cytokine signaling 2.After treatment with 40 and 60 mg/L ginkgolide B,cells were large,with long processes.Moreover,the proportions of neuron-specific enolase-,glial fibrillary acid protein-and suppressor of cytokine signaling 2-positive cells increased.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.Six hours after ischemia,ginkgolide B(20 mg/kg) was intraperitoneally injected,once a day.Zea Longa's method was used to assess neurological function.Immunohistochemistry was performed to evaluate the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells.Real-time quantitative polymerase chain reaction was used to measure m RNA expression of brain-derived neurotrophic factor and epidermal growth factor.Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2.Ginkgolide B decreased the neurological deficit score,increased the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells,increased the m RNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra.Together,the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury.
基金supported by the grant from the Science and Technology Department of Zhejiang Province(2015C34007).
文摘Background:A rapid elevation of post-ischemic circulating hepatocyte growth factor(HGF)levels has been reported in acute vascular disease including stroke.However,the impact of transient ischemic attack(TIA)on circulating HGF has never been studied.Methods:Patients with an onset of either stroke or TIA within the past 30 days were enrolled.Based on the ischemic event,the patients were divided into a stroke group and a TIA group.Blood samples were collected at enrollment and at follow-up visits at one,three,and six months until a recurrent cerebral ischemic event.Plasma levels of HGF were measured using an enzyme-linked immunosorbent assay and logarithmically transformed to eliminate skewness.Results:Thirty-six patients were enrolled in the study,with 20 in the stroke group and 16 in the TIA group.The dynamic HGF levels post-ischemia showed distinct patterns between the two groups.A significant decrease of HGF levels was observed in the stroke group,from 2.62±0.18 ng/mL within 30 days after stroke to 2.41±0.22 ng/mL beyond 30 days(P=0.026);however,no significant change was found in the TIA group(2.22±0.17 ng/mL vs.2.19±0.16 ng/mL,P=0.990).A multivariate regression analysis showed a last event of stroke and a comorbidity of systemic atherosclerotic disease(SAD)were independently associated with higher levels of HGF.Subgroup analyses showed HGF levels decreased from 2.64±0.22 ng/mL within 30 days after stroke to 2.36±0.18 ng/mL beyond 30 days in patients without SAD(P=0.008),but not in patients with SAD(P=0.700).Conclusion:Our data indicate that in patients without SAD,circulating HGF is a potential biomarker to distinguish between stroke and TIA.