Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises...Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke.Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit.In this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia.Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery.Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery.First,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling.Second,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons.Thus,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.展开更多
Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to conti...Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.展开更多
Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived e...Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.展开更多
Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in ...Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen Neu N, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ？ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke.展开更多
目的研究高压氧联合神经生长因子局部注射对骨质疏松性骨折延迟愈合患者血清黏附因子及微循环指标表达的影响。方法选取骨质疏松性骨折有延迟愈合患者84例,分为对照组和观察组各42例。两组均行常规治疗。观察组除此之外,进行高压氧疗,...目的研究高压氧联合神经生长因子局部注射对骨质疏松性骨折延迟愈合患者血清黏附因子及微循环指标表达的影响。方法选取骨质疏松性骨折有延迟愈合患者84例,分为对照组和观察组各42例。两组均行常规治疗。观察组除此之外,进行高压氧疗,并在骨折周围肌肉注射鼠神经生长因子。比较两组患者骨折愈合情况,同时比较两组治疗前后血液流变学指标(红细胞聚集指数、血浆黏度、红细胞刚性指数),血清黏附因子[血清人可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)]及骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)水平,转化生长因子(transforming growth factor β1,TGF-β1)、胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)、血小板衍生生长因子(platelet derived growth factor,PDGF)水平及OPG/RANKL蛋白表达。结果治疗后1、2、3个月及6个月,观察组骨折愈合率均显著高于对照组,差异具有统计学意义( P <0.05)。治疗后,观察组患者的红细胞聚集指数、血浆黏度、红细胞刚性指数水平均明显优于对照组,差异具有统计学意义( P <0.01);观察组sICAM-1、BMP-2、sVCAM-1水平显著高于对照组,差异具有统计学意义( P <0.01);观察组TGF-β1、IGF-1及PDGF水平显著高于对照组,差异具有统计学意义( P <0.01);观察组OPG/RANKL蛋白表达显著高于对照组,差异具有统计学意义( P <0.05)。结论高压氧联合神经生长因子局部注射能够显著改善骨质疏松性骨折延迟愈合患者血清黏附因子及微循环指标,促进骨折愈合,值得在临床推广。展开更多
基金supported by a Grant-in-Aid for Scientific Research(Research Project No.15K19478 and 18K07493,both to MK)Japan Science and Technology Agency(JST),the Translational Research program+7 种基金Strategic Promotion for practical application of Innovative medical Technology(TR-SPRINT)supported by Japan Agency for Medical Research and Development(AMED)under Grant No.JP19lm0203023a grant from Takeda Science Foundationthe Bayer Scholarship for Cardiovascular ResearchJapan Cardiovascular Research FoundationAstellas Foundation for Research on Metabolic DisordersYoung Investigator Okamoto AwardMedical Research Encouragement Prize of the Japan Medical Association(to MK)supported by a grant from Tsubaki Memorial Foundation(to MH and IN)
文摘Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke.Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit.In this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia.Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery.Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery.First,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling.Second,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons.Thus,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.
文摘Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.
基金sponsored by CONACYT scholarship#487713Fondo Mixto de Ciencia y Tecnología del Estado de Jalisco grant JAL-2014-0-250508
文摘Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.
基金supported by the Korea Health Technology R&D Project,Ministry of Health & Welfare(HI12C0381),Republic of Korea
文摘Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen Neu N, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ？ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke.
基金This work was supported by Grant from National Natural ScienceFoundation of China (30200291, 30170300) and Natural Science Foundation of Shaanxi Province,China(2002C250,2001SM63).
文摘目的研究高压氧联合神经生长因子局部注射对骨质疏松性骨折延迟愈合患者血清黏附因子及微循环指标表达的影响。方法选取骨质疏松性骨折有延迟愈合患者84例,分为对照组和观察组各42例。两组均行常规治疗。观察组除此之外,进行高压氧疗,并在骨折周围肌肉注射鼠神经生长因子。比较两组患者骨折愈合情况,同时比较两组治疗前后血液流变学指标(红细胞聚集指数、血浆黏度、红细胞刚性指数),血清黏附因子[血清人可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)]及骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)水平,转化生长因子(transforming growth factor β1,TGF-β1)、胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)、血小板衍生生长因子(platelet derived growth factor,PDGF)水平及OPG/RANKL蛋白表达。结果治疗后1、2、3个月及6个月,观察组骨折愈合率均显著高于对照组,差异具有统计学意义( P <0.05)。治疗后,观察组患者的红细胞聚集指数、血浆黏度、红细胞刚性指数水平均明显优于对照组,差异具有统计学意义( P <0.01);观察组sICAM-1、BMP-2、sVCAM-1水平显著高于对照组,差异具有统计学意义( P <0.01);观察组TGF-β1、IGF-1及PDGF水平显著高于对照组,差异具有统计学意义( P <0.01);观察组OPG/RANKL蛋白表达显著高于对照组,差异具有统计学意义( P <0.05)。结论高压氧联合神经生长因子局部注射能够显著改善骨质疏松性骨折延迟愈合患者血清黏附因子及微循环指标,促进骨折愈合,值得在临床推广。
