Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of...Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.展开更多
Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is...Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is underesti- mated because it often has a mild and transient nature. The etiology of ischemic colitis is multifactorial and the clinical presentation variable. The diagnosis is based on a combination of clinical suspicion, radiographic, endo- scopic and histological findings. Therapy and outcome depends on the severity of the disease. Most cases of the non-gangrenous form are transient and resolve spontaneously without complications. On the other hand, high morbidity and mortality and urgent operative intervention are the hallmarks of gangrenous ischemic colitis.展开更多
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
Objective To investigate whether pretreatment with repeated electroacupuncture (EA)at the Baihui acupoint could induce ischemic tolerance against transient focal cerebral ischemic injury in rats. Methods Thirty mal...Objective To investigate whether pretreatment with repeated electroacupuncture (EA)at the Baihui acupoint could induce ischemic tolerance against transient focal cerebral ischemic injury in rats. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into 3 groups (n=10 for each): the control group consisted of animals receiving no treatment, the isoflurane (ISO) group had animals that inhaled 1.5% isoflurane for 30 min a day for 5 days, and animals in the EA group received electroacupuncture at the Baihui acupoint for 30 min a day for 5 days under 1.5% isoflurane anesthesia. Twenty-four hours after the last treatment, the middle cerebral artery was occluded with No. 3 nylon monofilament for 120 min. The neurological outcomes were evaluated 24 h after reperfusion. The infarct volumes were then assessed using 2% triphenyltetrazolium chloride staining after the neurological outcome evaluation. Results The neurological deficit score (NDS) of the EA group was lower than that of the ISO group and the control group , P<0.05. The infarct volume of the EA group (38.3±25.4 mm 3) was significantly smaller than that of the control group (220.5±66.0 mm 3) and the ISO group (168.6±57.6 mm 3) 24 h after reperfusion. Conclusion Electroacupuncture at the Baihui acupoint 30 min a day for 5 days significantly reduces neurological injury induced by transient middle cerebral artery occlusion.展开更多
This study was designed to determine if repeated hyperbaric oxygen (HBO) exposure induces ischemic tolerance in focal cerebral ischemia Methods Sixty male SD rats were used in this study Thirty animals underw...This study was designed to determine if repeated hyperbaric oxygen (HBO) exposure induces ischemic tolerance in focal cerebral ischemia Methods Sixty male SD rats were used in this study Thirty animals underwent transient middle cerebral artery occlusion (MCAO) and the other thirty permanent MCAO model The rats were randomly allocated to 3 sub-groups: control group (n=10), HBO-3 group (n=10), and HBO-5 group (n=10) The animals in HBO-3 and HBO-5 groups received 1*!hour hyperbaric oxygenation at 2 5 atmosphere absolute (ATA) in 100% oxygen every day for 3 and 5 days, respectively The animals in the control group received sham treatments 24*!hours after the last HBO, transient MCAO (120 min) and permanent MCAO were induced by introducing a 3-0 nylon monofilament suture through internal carotid artery based on the Koizumi technique The neurological outcome was evaluated until 24*!hours after reperfusion in transient MCAO rats and ischemia in permanent MCAO rats The infarct volume was then assessed by TTC staining Results In transient MCAO rats, the neurological outcome in both the HBO-3 and HBO-5 groups was better than that of the control group ( P <0 05 and 0 001) The infarct volume decreased from 171 5±113*!mm 3 to 40 6±49 9*!mm 3 ( P <0 05) in the HBO-3 group and 16 2±28 8*!mm 3 ( P <0 01) in the HBO-5 group There were no significant differences in neurological outcome and infarct volume among the three groups in permanent MCAO rats Conclusions The present study demonstrated that HBO preconditioning can induce ischemic tolerance in transient not permanent MCAO rats in a “dose-dependent' manner展开更多
Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether acti- vation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the po...Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether acti- vation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the potential role and possible signaling pathway of autophagy in neuronal survival after cerebral ischemia and proposes that autophagy has dual effects.展开更多
Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustraz...Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administra- tion, and the most effective mode of administration for clinical treatment of cerebral ischemia/ reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine admin- istration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[（1,1-dimethylethyl）oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC 195 after cerebral ischemia were better than ligustrazine.展开更多
AIthough atherosclerosis has been considered to be multi-factorial disease in which genetic,environmental, metabolic factors have been implicated, the gaps remain in our knowledge of the etiopathogenesis of atheroscle...AIthough atherosclerosis has been considered to be multi-factorial disease in which genetic,environmental, metabolic factors have been implicated, the gaps remain in our knowledge of the etiopathogenesis of atherosclerosis. There is mounting evidence that inflammation plays an important role in the initiation, development as well as evolution of atherosclerosis, suggesting that atherosclerosis is an inflammation disease. Although triggers and pathways of inflammation are probably multiple and different in different clinical settings, the data from animals as well as humans including our groups indicated that an inflammatory process was involved in all stages of atherosclerosis appeared in different clinical entities.展开更多
基金supported by the Natural Science Foundation of Shanghai of China,No.17ZR1425800(to KYL)the Shanghai Pudong District Health Bureau of China,No.PDZX2017-25(to KYL)
文摘Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.
文摘Ischemic colitis is the most common form of ischemic injury of the gastrointestinal tract and can present either as an occlusive or a non-occlusive form. It accounts for 1 in 1000 hospitalizations but its incidence is underesti- mated because it often has a mild and transient nature. The etiology of ischemic colitis is multifactorial and the clinical presentation variable. The diagnosis is based on a combination of clinical suspicion, radiographic, endo- scopic and histological findings. Therapy and outcome depends on the severity of the disease. Most cases of the non-gangrenous form are transient and resolve spontaneously without complications. On the other hand, high morbidity and mortality and urgent operative intervention are the hallmarks of gangrenous ischemic colitis.
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.
基金ThisstudywassupportedinpartbyagrantfromtheNationalNaturalScienceFoundationofChina (No 30 170 90 7)
文摘Objective To investigate whether pretreatment with repeated electroacupuncture (EA)at the Baihui acupoint could induce ischemic tolerance against transient focal cerebral ischemic injury in rats. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into 3 groups (n=10 for each): the control group consisted of animals receiving no treatment, the isoflurane (ISO) group had animals that inhaled 1.5% isoflurane for 30 min a day for 5 days, and animals in the EA group received electroacupuncture at the Baihui acupoint for 30 min a day for 5 days under 1.5% isoflurane anesthesia. Twenty-four hours after the last treatment, the middle cerebral artery was occluded with No. 3 nylon monofilament for 120 min. The neurological outcomes were evaluated 24 h after reperfusion. The infarct volumes were then assessed using 2% triphenyltetrazolium chloride staining after the neurological outcome evaluation. Results The neurological deficit score (NDS) of the EA group was lower than that of the ISO group and the control group , P<0.05. The infarct volume of the EA group (38.3±25.4 mm 3) was significantly smaller than that of the control group (220.5±66.0 mm 3) and the ISO group (168.6±57.6 mm 3) 24 h after reperfusion. Conclusion Electroacupuncture at the Baihui acupoint 30 min a day for 5 days significantly reduces neurological injury induced by transient middle cerebral artery occlusion.
基金ThisstudywassupportedinpartbyagrantfromtheNationalNaturalScienceFoundationofChina (No 396 70 6 99)
文摘This study was designed to determine if repeated hyperbaric oxygen (HBO) exposure induces ischemic tolerance in focal cerebral ischemia Methods Sixty male SD rats were used in this study Thirty animals underwent transient middle cerebral artery occlusion (MCAO) and the other thirty permanent MCAO model The rats were randomly allocated to 3 sub-groups: control group (n=10), HBO-3 group (n=10), and HBO-5 group (n=10) The animals in HBO-3 and HBO-5 groups received 1*!hour hyperbaric oxygenation at 2 5 atmosphere absolute (ATA) in 100% oxygen every day for 3 and 5 days, respectively The animals in the control group received sham treatments 24*!hours after the last HBO, transient MCAO (120 min) and permanent MCAO were induced by introducing a 3-0 nylon monofilament suture through internal carotid artery based on the Koizumi technique The neurological outcome was evaluated until 24*!hours after reperfusion in transient MCAO rats and ischemia in permanent MCAO rats The infarct volume was then assessed by TTC staining Results In transient MCAO rats, the neurological outcome in both the HBO-3 and HBO-5 groups was better than that of the control group ( P <0 05 and 0 001) The infarct volume decreased from 171 5±113*!mm 3 to 40 6±49 9*!mm 3 ( P <0 05) in the HBO-3 group and 16 2±28 8*!mm 3 ( P <0 01) in the HBO-5 group There were no significant differences in neurological outcome and infarct volume among the three groups in permanent MCAO rats Conclusions The present study demonstrated that HBO preconditioning can induce ischemic tolerance in transient not permanent MCAO rats in a “dose-dependent' manner
基金supported by grants from the project of National Natural Science Foundation of China,No.31171014 and 31371065the project of Science and Technology Commission of Board of Health of Shanghai,China,No.20134125the Key Specialty(disease) Declaration of Pudong New Area’s Health System
文摘Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether acti- vation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the potential role and possible signaling pathway of autophagy in neuronal survival after cerebral ischemia and proposes that autophagy has dual effects.
基金supported by a grant from the Health and Family Planning Commission of Heilongjiang Province Research Project in China,No.2014-195the Education Department Science and Technology Foundation of Heilongjiang Province in China,No.12531741the Natural Science Foundation of Heilongjiang Province of China,No.H2015083
文摘Ligustrazine （2,3,5,6-tetramethylpyrazine） is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mecha- nism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administra- tion, and the most effective mode of administration for clinical treatment of cerebral ischemia/ reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine admin- istration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[（1,1-dimethylethyl）oxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC 195 after cerebral ischemia were better than ligustrazine.
文摘AIthough atherosclerosis has been considered to be multi-factorial disease in which genetic,environmental, metabolic factors have been implicated, the gaps remain in our knowledge of the etiopathogenesis of atherosclerosis. There is mounting evidence that inflammation plays an important role in the initiation, development as well as evolution of atherosclerosis, suggesting that atherosclerosis is an inflammation disease. Although triggers and pathways of inflammation are probably multiple and different in different clinical settings, the data from animals as well as humans including our groups indicated that an inflammatory process was involved in all stages of atherosclerosis appeared in different clinical entities.
