Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell...Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.展开更多
An emerging concept termed the neurovascular unit(NVU)underlines neurovascular coupling.It has been reported that NVU impairment can result in neurodegenerative diseases,such as Alzheimer's disease and Parkinson&#...An emerging concept termed the neurovascular unit(NVU)underlines neurovascular coupling.It has been reported that NVU impairment can result in neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.Aging is a complex and irreversible process caused by programmed and damage-related factors.Loss of biological functions and increased susceptibility to additional neurodegenerative diseases are major characteristics of aging.In this review,we describe the basics of the NVU and discuss the effect of aging on NVU basics.Furthermore,we summarize the mechanisms that increase NVU susceptibility to neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.Finally,we discuss new treatments for neurodegenerative diseases and methods of maintaining an intact NVU that may delay or diminish aging.展开更多
Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)i...Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.展开更多
Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open or...Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81974207(to JH),82001383(to DW)the Special Clinical Research Project of Health Profession of Shanghai Municipal Health Commission,No.20204Y0076(to DW)。
文摘Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective effects.However,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently increased.In this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning techniques.We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month.This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation.Furthermore,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved caspase-3.Therefore,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.
基金supported by the Construction Project of Capacity Improvement Plan for Chongqing Municipal Health Commission affiliated unit [Grant No. (2019NLTS001) -ZS03174]the operating grant to Chongqing Key Laboratory of Neurodegenerative Diseases (Grant No.1000013)+1 种基金Chongqing Talent Project (Grant No.2000062),Overseas Students entrepreneurial fund (Grant No.2000079)Plan for High-level Talent Introduction (Grant No.2000055).
文摘An emerging concept termed the neurovascular unit(NVU)underlines neurovascular coupling.It has been reported that NVU impairment can result in neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.Aging is a complex and irreversible process caused by programmed and damage-related factors.Loss of biological functions and increased susceptibility to additional neurodegenerative diseases are major characteristics of aging.In this review,we describe the basics of the NVU and discuss the effect of aging on NVU basics.Furthermore,we summarize the mechanisms that increase NVU susceptibility to neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.Finally,we discuss new treatments for neurodegenerative diseases and methods of maintaining an intact NVU that may delay or diminish aging.
基金supported by grants from the National Natural Science Foundation of China,No.81971231(to JL)Liaoning Revitalization Talents Program,No.XLYC1907178(to JL)。
文摘Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.
基金This work was supported by Project of Natural Science Foundation of Shandong province(No.ZR2020MH343).
文摘Background:Compatibility is a characteristic of the clinical application of traditional Chinese medicine,often leading to enhanced therapeutic effects.In the treatment of cerebral ischemia,blood-activating and open orifices herbs are frequently used individually;however,their combination is not commonly practiced.This study aims to investigate the impact of combining safflower and borneol as examples of open orifices herbs and blood-activating herbs on the neurovascular unit in rats with ischemic stroke.The objective is to determine whether this combination exhibits superior therapeutic efficacy compared to using borneol or safflower alone while exploring its underlying mechanism.These findings may provide novel insights for clinical treatments.Methods:SD male rats were randomly divided into 6 groups:sham operation group,model group,borneol group(0.1 g/kg),safflower group(5 g/kg),borneol combined with safflower group(0.1 g/kg+5 g/kg)and nimodipine group(0.01 g/kg).The middle cerebral artery cerebral ischemia(MCAO)model were prepared after continuous intragastric administration for 7 days in each group,the neurological function of each group were scored 24h after operation,and water content in brain tissue were measured by weighing method.The activity of superoxide dismutase(SOD)and the contents of nitric oxide(NO)and malondialdehyde(MDA)in brain tissue and serum were determined by spectrophotometry,and the mRNA expressions of matrix metalloproteinase 2(MMP-2),tight junction protein 1(ZO-1),vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF)were detected by Real time PCR.Result:Compared with the model group,the group treated with borneol combined with safflower exhibited a significant decrease in the neural function score of MCAO rats(P<0.01).Additionally,it led to a reduction in brain tissue water content(P<0.01),elevated SOD activity,and reduced levels of NO and MDA in both serum and brain tissue(P<0.01 or P<0.05).Moreover,this treatment resulted in a decrease in the mRNA expression of MMP-2 and an increase in ZO-1 in brain tissue,along with an increase in the mRNA expression of VEGF and BDNF(P<0.01).Conclusion:Borneol combined with safflower demonstrates a protective effect on the neurovascular unit in rats with ischemic stroke.This effect is likely associated with increased SOD activity,reduced MDA and NO content in both serum and brain tissue of MCAO rats,and a decrease in MMP-2 mRNA expression in brain tissue,coupled with an increase in ZO-1,VEGF,and BDNF mRNA expression.These effects were superior to those observed with borneol or safflower administered alone.
