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
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
目的探讨左西孟旦治疗老年缺血性心肌病所致急性失代偿性心力衰竭患者的疗效和安全性。方法选择老年缺血性心肌病所致急性失代偿性心力衰竭患者60例,根据治疗方法随机分为左西孟旦组30例和常规治疗组30例。2组患者治疗前和治疗后1周分...目的探讨左西孟旦治疗老年缺血性心肌病所致急性失代偿性心力衰竭患者的疗效和安全性。方法选择老年缺血性心肌病所致急性失代偿性心力衰竭患者60例,根据治疗方法随机分为左西孟旦组30例和常规治疗组30例。2组患者治疗前和治疗后1周分别测定血压、心率、左心室射血分数、血浆N末端钠尿肽前体和肌酐水平,并进行疗效和安全性比较。结果左西孟旦组治疗后左心室射血分数明显高于常规治疗组,血浆N末端钠尿肽前体水平明显低于常规治疗组(36.5%vs 34.0%,1872.9ng/L vs 2499.6ng/L,P<0.05)。左西孟旦组与常规治疗组治疗后血压、心率和肌酐水平比较,差异无统计学意义(P>0.05)。结论老年缺血性心肌病导致的急性失代偿性心力衰竭患者使用左西孟旦后,左心室射血分数升高,N末端钠尿肽前体水平降低,而血压、心率和肾功能并无异常,证实了左西孟旦治疗老年缺血性心肌病导致的急性失代偿性心力衰竭患者安全有效。展开更多
Hypoperfusion injury related to blood pressure decrease in acute hypertensive intracerebral hemorrhage continues to be a controversial topic. Aggressive treatment is provided with the intent to stop the ongoing bleedi...Hypoperfusion injury related to blood pressure decrease in acute hypertensive intracerebral hemorrhage continues to be a controversial topic. Aggressive treatment is provided with the intent to stop the ongoing bleeding. However, there may be additional factors, including autoregulation and increased intracranial pressure, that may limit this approach. We present here a case of acute hypertensive intracerebral hemorrhage, in which aggressive blood pressure management to levels within the normal range led to global cerebral ischemia within multiple border zones. Global cerebral ischemia may be of concern in the management of hypertensive hemorrhage in the presence of premorbid poorly controlled blood pressure and increased intracranial pressure.展开更多
目的探讨急性缺血性脑卒中(AIS)经阿替普酶静脉溶栓治疗后出血性转化(HT)的影响因素。方法选取2015-01—2017-07作者医院收治的经阿替普酶静脉溶栓治疗的AIS患者348例,根据阿替普酶静脉溶栓后是否发生HT将患者分为出血组和未出血组。回...目的探讨急性缺血性脑卒中(AIS)经阿替普酶静脉溶栓治疗后出血性转化(HT)的影响因素。方法选取2015-01—2017-07作者医院收治的经阿替普酶静脉溶栓治疗的AIS患者348例,根据阿替普酶静脉溶栓后是否发生HT将患者分为出血组和未出血组。回顾性收集所有研究对象的临床资料(人口统计学、血管危险因素和实验室检查指标等),采用多因素Logistic回归分析探讨ALS经阿替普酶静脉溶栓治疗后发生HT的独立危险因素。结果出血组32例,未出血组316例。两组患者间基线血糖、基线美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分、发病至静脉溶栓治疗时间、心房颤动史、溶栓24h后收缩压以及抗血小板药物服用史差异均有统计学意义(均P<0.05)。多因素Logistic回归分析结果显示,基线血糖(OR=3.781,95%CI:1.851~11.765)、基线NIHSS评分(OR=2.678,95%CI:1.384~10.441)、发病至静脉溶栓治疗时间(OR=2.436,95%CI:1.324~4.488)、心房颤动史(OR=4.538,95%CI:2.036~14.132)和溶栓24h后收缩压(OR=1.581,95%CI:1.071~6.415)是发生HT的独立危险因素(均P<0.05)。结论基线血糖、基线NIHSS评分、发病至静脉溶栓治疗时间、心房颤动史和溶栓24h后收缩压是脑梗死患者静脉溶栓后发生HT的危险因素。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.
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.
文摘目的探讨左西孟旦治疗老年缺血性心肌病所致急性失代偿性心力衰竭患者的疗效和安全性。方法选择老年缺血性心肌病所致急性失代偿性心力衰竭患者60例,根据治疗方法随机分为左西孟旦组30例和常规治疗组30例。2组患者治疗前和治疗后1周分别测定血压、心率、左心室射血分数、血浆N末端钠尿肽前体和肌酐水平,并进行疗效和安全性比较。结果左西孟旦组治疗后左心室射血分数明显高于常规治疗组,血浆N末端钠尿肽前体水平明显低于常规治疗组(36.5%vs 34.0%,1872.9ng/L vs 2499.6ng/L,P<0.05)。左西孟旦组与常规治疗组治疗后血压、心率和肌酐水平比较,差异无统计学意义(P>0.05)。结论老年缺血性心肌病导致的急性失代偿性心力衰竭患者使用左西孟旦后,左心室射血分数升高,N末端钠尿肽前体水平降低,而血压、心率和肾功能并无异常,证实了左西孟旦治疗老年缺血性心肌病导致的急性失代偿性心力衰竭患者安全有效。
文摘Hypoperfusion injury related to blood pressure decrease in acute hypertensive intracerebral hemorrhage continues to be a controversial topic. Aggressive treatment is provided with the intent to stop the ongoing bleeding. However, there may be additional factors, including autoregulation and increased intracranial pressure, that may limit this approach. We present here a case of acute hypertensive intracerebral hemorrhage, in which aggressive blood pressure management to levels within the normal range led to global cerebral ischemia within multiple border zones. Global cerebral ischemia may be of concern in the management of hypertensive hemorrhage in the presence of premorbid poorly controlled blood pressure and increased intracranial pressure.
文摘目的探讨急性缺血性脑卒中(AIS)经阿替普酶静脉溶栓治疗后出血性转化(HT)的影响因素。方法选取2015-01—2017-07作者医院收治的经阿替普酶静脉溶栓治疗的AIS患者348例,根据阿替普酶静脉溶栓后是否发生HT将患者分为出血组和未出血组。回顾性收集所有研究对象的临床资料(人口统计学、血管危险因素和实验室检查指标等),采用多因素Logistic回归分析探讨ALS经阿替普酶静脉溶栓治疗后发生HT的独立危险因素。结果出血组32例,未出血组316例。两组患者间基线血糖、基线美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分、发病至静脉溶栓治疗时间、心房颤动史、溶栓24h后收缩压以及抗血小板药物服用史差异均有统计学意义(均P<0.05)。多因素Logistic回归分析结果显示,基线血糖(OR=3.781,95%CI:1.851~11.765)、基线NIHSS评分(OR=2.678,95%CI:1.384~10.441)、发病至静脉溶栓治疗时间(OR=2.436,95%CI:1.324~4.488)、心房颤动史(OR=4.538,95%CI:2.036~14.132)和溶栓24h后收缩压(OR=1.581,95%CI:1.071~6.415)是发生HT的独立危险因素(均P<0.05)。结论基线血糖、基线NIHSS评分、发病至静脉溶栓治疗时间、心房颤动史和溶栓24h后收缩压是脑梗死患者静脉溶栓后发生HT的危险因素。
