Spinal cord ischemia(SCI),a frequent complication following open and endovascular thoracoabdominal aortic aneurysm(TAAA)repair,is a feared complication with relevant impact on a patient's quality of life.In the ea...Spinal cord ischemia(SCI),a frequent complication following open and endovascular thoracoabdominal aortic aneurysm(TAAA)repair,is a feared complication with relevant impact on a patient's quality of life.In the early days of open TAAA repair,more than one third of the patients suffered from SCI.Nowadays,due to improved preventive measures and the option of staged endovascular TAAA repair,10%of all patients are affected by spinal cord problems after TAAA repair(Rocha et al.,2020).展开更多
背景:激素性股骨头缺血坏死的发病机制尚不明确,可能与内质网应激有关,控制内质网应激信号通路可能调控细胞的自噬与凋亡,对该病具有一定的防治作用。目的:通过探讨内质网应激与激素引起的细胞自噬、细胞凋亡的相互关系,总结内质网应激...背景:激素性股骨头缺血坏死的发病机制尚不明确,可能与内质网应激有关,控制内质网应激信号通路可能调控细胞的自噬与凋亡,对该病具有一定的防治作用。目的:通过探讨内质网应激与激素引起的细胞自噬、细胞凋亡的相互关系,总结内质网应激在激素性股骨头缺血坏死发病机制中的研究进展。方法:检索2000至2020年相关文献,以“内质网应激,股骨头坏死,未折叠蛋白反应,糖皮质激素,自噬,凋亡,缺血”为中文检索词检索CNKI、万方、维普数据库;以“endoplasmic reticulum stress,femur head necrosis,unfolded protein response,glucocorticoid,autophagy,apoptosis,ischaemia”为英文检索词检索PubMed、Web of science数据库。排除重复和较陈旧的文献及Meta分析,共81篇文献符合纳入标准。结果与结论:①未折叠蛋白反应为缓解内质网应激引发的3条下游信号通路可使细胞发生自噬和凋亡;②内质网应激与激素诱导的细胞自噬和凋亡及股骨头缺血有密切联系;③内质网应激可能是激素性股骨头缺血坏死发生过程中的病理环节,激素通过让细胞缺血缺氧激发内质网应激进而诱导细胞的自噬与凋亡,最终导致股骨头坏死。展开更多
Subcortical ischemic white matter injury(SIWMI),pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging,is a common cause of cognitive decline in elderly.Despite its high...Subcortical ischemic white matter injury(SIWMI),pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging,is a common cause of cognitive decline in elderly.Despite its high prevalence,it remains unknown how various components of the white matter degenerate in response to chronic ischemia.This incomplete knowledge is in part due to a lack of adequate animal model.The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components.The SIWMI animal models are categorized into 1)chemically induced SIWMI models,2)vascular occlusive SIWMI models,and 3)SIWMI models with comorbid vascular risk factors.Chemically induced models display consistent lesions in predetermined areas of the white matter,but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities.Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified.When combined with comorbid vascular risk factors(specifically hypertension),however,they can produce progressive and definitive white matter lesions including diffuse rarefaction,demyelination,loss of oligodendrocytes,and glial activation,which are by far the closest to those found in human white matter hyperintensities lesions.However,considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models.In the meantime,in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury.Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities.展开更多
Extremely low frequency electromagnetic fields(ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood.In this s...Extremely low frequency electromagnetic fields(ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood.In this study, we established rat models of middle cerebral artery occlusion/reperfusion.One day after modeling, a group of rats were treated with ELF-EMF(50 Hz, 1 mT) for 2 hours daily on 28 successive days.Our results showed that rats treated with ELF-EMF required shorter swimming distances and latencies in the Morris water maze test than those of untreated rats.The number of times the platform was crossed and the time spent in the target quadrant were greater than those of untreated rats.The number of BrdU~+/NeuN~+ cells, representing newly born neurons, in the hippocampal subgranular zone increased more in the treated than in untreated rats.Up-regulation in the expressions of Notch1, Hes1, and Hes5 proteins, which are the key factors of the Notch signaling pathway, was greatest in the treated rats.These findings suggest that ELF-EMF can enhance hippocampal neurogenesis of rats with cerebral ischemia, possibly by affecting the Notch signaling pathway.The study was approved by the Institutional Ethics Committee of Sichuan University, China(approval No.2019255A) on March 5, 2019.展开更多
Infusion of the colloid hydroxyethylstarch has been used for volume substitution to maintain hemodynamics and microcirculation after e.g., severe blood loss.In the last decade it was revealed that hydroxyethylstarch c...Infusion of the colloid hydroxyethylstarch has been used for volume substitution to maintain hemodynamics and microcirculation after e.g., severe blood loss.In the last decade it was revealed that hydroxyethylstarch can aggravate acute kidney injury, especially in septic patients.Because of the serious risk for critically ill patients, the administration of hydroxyethylstarch was restricted for clinical use.Animal studies and recently published in vitro experiments showed that hydroxyethylstarch might exert protective effects on the blood-brain barrier.Since the prevention of blood-brain barrier disruption was shown to go along with the reduction of brain damage after several kinds of insults, we revisit the topic hydroxyethylstarch and discuss a possible niche for the application of hydroxyethylstarch in acute brain injury treatment.展开更多
Neurodegeneration in the brain after ischemia with reperfusion mimicking the neuropathology of Alzheimer's disease:Brain ischemia with reperfusion,which is one of the main causes of morbidity and mortality in the ...Neurodegeneration in the brain after ischemia with reperfusion mimicking the neuropathology of Alzheimer's disease:Brain ischemia with reperfusion,which is one of the main causes of morbidity and mortality in the world,triggers various neuropathological changes characteristic for Alzheimer's disease(AD)such as increased blood-brain barrier permeability,excitotoxicity,necrosis,autophagy,mitophagy,apoptosis,neuroinflammation,amyloid plaques,neurofibrillary tangles,cerebral vessel pathology,and brain atrophy that lead to the death of neurons,deteriorating motor,sensory and cognitive functions(Figure 1)(Kato et al.,1988;Wisniewski et al.,1995;Van Groen et al.,2005;Kocki et al.,2015;Ułamek-Koziołet al.,2016,2017,2019).Brain ischemia is recognized as a major contributor to the dysfunction of an aging brain and the development of neurodegenerative diseases,including AD(Pluta,2019).展开更多
Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of t...Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects.In this study,EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed.Except for the normal group,rats in other groups were fed a high-fat diet throughout the whole experiment.Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks.Middle cerebral artery thrombus models were induced by pasting 50%FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group.EA1 group rats received EA at bilateral ST40(Fenglong)for 7 days before the thrombosis.Rats in the EA1 and EA2 groups received EA at GV20(Baihui)and bilateral ST40 for 14 days after model establishment.Neuronal health was assessed by hematoxylin-eosin staining in the brain.Hyperlipidemia was assessed by biochemical methods that measured total cholesterol,triglyceride,low-density lipoprotein and high-density lipoprotein in blood sera.Behavioral analysis was used to confirm the establishment of the model.Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region.The results demonstrated that,compared with the model group,blood lipid levels significantly decreased,glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups.The repair effect was superior in the EA1 group than in the EA2 group.These findings confirm that EA can reduce blood lipid,inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after 展开更多
Apoptosis is an important programmed cell death process involved in ischemia/reperfusion injury.MicroRNAs are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ische...Apoptosis is an important programmed cell death process involved in ischemia/reperfusion injury.MicroRNAs are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ischemia and reperfusion injury.However,whether miR-670 can regulate cell growth and death in cerebral ischemia/reperfusion and the underlying mechanism are poorly understood.In this study,we established mouse models of transient middle artery occlusion and Neuro 2a cell models of oxygen-glucose deprivation and reoxygenation to investigate the potential molecular mechanism by which miR-670 exhibits its effects during cerebral ischemia/reperfusion injury both in vitro and in vivo.Our results showed that after ischemia/reperfusion injury,miR-670 expression was obviously increased.After miR-670 expression was inhibited with an miR-670 antagomir,cerebral ischemia/reperfusion injury-induced neuronal death was obviously reduced.When miR-670 overexpression was induced by an miR-670 agomir,neuronal apoptosis was increased.In addition,we also found that miR-670 could promote Yap degradation via phosphorylation and worsen neuronal apoptosis and neurological deficits.Inhibition of miR-670 reduced neurological impairments after cerebral ischemia/reperfusion injury.These results suggest that microRNA-670 aggravates cerebral ischemia/reperfusion injury through the Yap pathway,which may be a potential target for treatment of cerebral ischemia/reperfusion injury.The present study was approved by the Institutional Animal Care and Use Committee of China Medical University on February 27,2017(IRB No.2017PS035K).展开更多
The discovery that new neurons are produced in some regions of the adult mammalian brain is a paradigm-shift in neuroscience research.These new-born cells are produced from neuroprogenitors mainly in the subventricula...The discovery that new neurons are produced in some regions of the adult mammalian brain is a paradigm-shift in neuroscience research.These new-born cells are produced from neuroprogenitors mainly in the subventricular zone at the margin of the lateral ventricle,subgranular zone in the hippocampal dentate gyrus and in the striatum,a component of the basal ganglia,even in humans.In the human hippocampus,neuroblasts are produced even in elderlies.The regulation of adult neurogenesis is a complex phenomenon involving a multitude of molecules,neurotransmitters and soluble factors released by different sources including glial cells.Microglia,the resident macrophages of the central nervous system,are considered to play an important role on the regulation of adult neurogenesis both in physiological and pathological conditions.Following stroke and other acute neural disorders,there is an increase in the numbers of neuroblast production in the neurogenic niches.Microglial activation is believed to display both beneficial and detrimental role on adult neurogenesis after stroke,depending on the activation level and brain location.In this article,we review the scientific evidence addressing the role of microglial activation on adult neurogenesis after ischemia.A comprehensive understanding of the microglial role after stroke and other neural disorders it is an important step for development of future therapies based on manipulation of adult neurogenesis.展开更多
<strong>Objectives:</strong> To identify the main risk factors of vascular cognitive impairment in patients with acute cerebral infarction by Meta-analysis, and provide references for the effective prevent...<strong>Objectives:</strong> To identify the main risk factors of vascular cognitive impairment in patients with acute cerebral infarction by Meta-analysis, and provide references for the effective prevention of the cognitive impairment in stroke patients. <strong>Methods:</strong> To retrieve the observational research literatures that refer to the risk factors of vascular cognitive impairment in patients with ischemic stroke, which are published on China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Chinese databases. The screening and data extraction of these literatures are independently completed by two researchers, who also give the quality evaluation of the literatures according to the evaluation criterion of the Australian JBI Evidence-Based Health Care Center. Then, Meta-analysis is conducted by using Revman5.3 software. <strong>Results:</strong> There are twenty-eight articles selected from 1507 literatures, with a total of 10,711 cases and 50 risk factors included. Among them, there are combined effects of ten factors which have statistical significance, such as infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetes mellitus, age, history of cerebral infarction, hyperlipoidemia and education level. The relational merging OR value and 95% CI between the type-variable factors and cognitive impairment are 3.25 (1.84, 5.76);2.98 (2.58, 3.45);2.79 (1.69, 4.59);2.35 (1.93, 2.85);2.25 (1.86, 2.71);2.14 (2.10, 2.18);1.82 (1.62, 2.03);1.54 (1.24, 1.92);1.45 (1.34, 1.56);0.83 (0.78, 0.89). <strong>Conclusion: </strong>Infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetesmellitus, age, history of cerebral infarction, hyperlipoidemia and low education level are the main risk factors for vascular cognitive impairment in patients with acute cerebral infarction. Clinical nursing staff should include it into the routine assessment of patients with acute cerebral infarction and actively prevent and intervene.展开更多
<strong>Background:</strong> <span style="font-family:""><span style="font-family:Verdana;">Beta-thalassemia is a hereditary haemoglobinopathy caused by defective hemog...<strong>Background:</strong> <span style="font-family:""><span style="font-family:Verdana;">Beta-thalassemia is a hereditary haemoglobinopathy caused by defective hemoglobin (Hb) </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-globin synthesis, leading to excess </span><i><span style="font-family:Verdana;">α</span></i><span style="font-family:Verdana;">-globin chains that cause hemolysis and impair erythropoiesis. Ischemia modified albumin (IMA) is not a signal protein and not generated in pro-inflammatory state alone but rather an end product of oxidative stress.</span><b><span style="font-family:Verdana;"> Objectives: </span></b><span style="font-family:Verdana;">The aim of the study was to evaluate ischemia modified albumin (IMA) and C-reactive protein (CRP) in children with </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-thalassemia major and its relation to different iron chelators. </span><b><span style="font-family:Verdana;">Patients and Methods: </span></b><span style="font-family:Verdana;">The study was carried on 40 children diagnosed as beta-thalassemia major recruited from the outpatient clinic and the pediatric department, at Al-Zahraa University Hospital, Faculty of medicine for Girls, Al-Azhar University and EL Minia Insurance Hospital. They were 20 male and 20 female, aged from 4 - 11 years. Another 40 apparently healthy children age and sex matched as control group. CRP and IMA were determined for all participants.</span><b><span style="font-family:Verdana;"> Results:</span></b><span style="font-family:Verdana;"> There were significant increases in serum CRP, IMA and ferritin levels in patients group compared to control group. There were significant decreases of IMA and CRP levels of thalassemic patients on chelation deferiprone (DFP) compared to deferasirox (DFX) P-value (<0.01) for each. There was a significant positive correlation between serum ferritin and both CRP and IMA levels in thalassemic childr展开更多
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
BACKGROUND The prognosis of acute mesenteric ischemia(AMI)caused by superior mesenteric venous thrombosis(SMVT)remains undetermined and early detection of transmural bowel infarction(TBI)is crucial.The predisposition ...BACKGROUND The prognosis of acute mesenteric ischemia(AMI)caused by superior mesenteric venous thrombosis(SMVT)remains undetermined and early detection of transmural bowel infarction(TBI)is crucial.The predisposition to develop TBI is of clinical concern,which can lead to fatal sepsis with hemodynamic instability and multi-organ failure.Early resection of necrotic bowel could improve the prognosis of AMI,however,accurate prediction of TBI remains a challenge for clinicians.When determining the eligibility for explorative laparotomy,the underlying risk factors for bowel infarction should be fully evaluated.AIM To develop and externally validate a nomogram for prediction of TBI in patients with acute SMVT.METHODS Consecutive data from 207 acute SMVT patients at the Wuhan Tongji Hospital and 89 patients at the Guangzhou Nanfang Hospital between July 2005 and December 2018 were included in this study.They were grouped as training and external validation cohort.The 207 cases(training cohort)from Tongji Hospital were divided into TBI and reversible intestinal ischemia groups based on the final therapeutic outcomes.Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for TBI using the training data,and a nomogram was subsequently developed.The performance of the nomogram was evaluated with respect to discrimination,calibration,and clinical usefulness in the training and external validation cohort.RESULTS Univariate and multivariate logistic regression analyses identified the following independent prognostic factors associated with TBI in the training cohort:The decreased bowel wall enhancement(OR=6.37,P<0.001),rebound tenderness(OR=7.14,P<0.001),serum lactate levels>2 mmol/L(OR=3.14,P=0.009)and previous history of deep venous thrombosis(OR=6.37,P<0.001).Incorporating these four factors,the nomogram achieved good calibration in the training set[area under the receiver operator characteristic curve(AUC)0.860;95%CI:0.771-0.925]and the external validation set(AUC 0.851展开更多
OBJECTIVE:To investigate the efficacy of Chinese medicines on Qi stagnation and blood stasis in rats with myocardial ischemia.METHODS:Fifty male Wistar rats were randomly divided into five groups(n=10)as follows:(a)sh...OBJECTIVE:To investigate the efficacy of Chinese medicines on Qi stagnation and blood stasis in rats with myocardial ischemia.METHODS:Fifty male Wistar rats were randomly divided into five groups(n=10)as follows:(a)sham operation(Sham),(b)myocardial ischemia(Model),(c)treatment that regulates Qi(Qi),(d)treatment that promotes blood circulation(Blood),(e)treatment that both regulates Qi and promotes blood circulation(QB).The rat model was established via activities restriction for 6 h followed by tail clamp stimulation for 5 mins every day for 7 d and occlusion left coronary anterior descending artery.Afterwards rats were treated with medicines that regulate Qi and/or promote blood circulation via gavage for 14 d.Behavioral parameters were evaluated using open field and elevated plus-maze tests.The tongue color and sublingual vein were visually examined.Blood flow perfusion of tongue and auricle were detected using PIMⅡ.The mesenteric microcirculation was examined via capillaroscopy,and hemodynamics was assessed using a polygraph system.Serum homocysteine(Hcy),creatine kinase isoenzyme(CKMB)levels and endothelin-1(ET-1)were measured.Hematoxylin and eosin staining and transmission electron microscopy were employed to detect the myocardial morphology and ultrastructure,respectively.RESULTS:Compared with findings in Sham group,rats in model group had coarse hair,dark mucosa of the lips and claw,low activity,and increased anxiety.Compared with findings in Model group,rats in the three treatment groups exhibited a lighter tongue color without an extended and varicose sublingual vein.There were significant increases of auricle blood flow perfusion in the Qi group and tongue bottom blood flow perfusion in the QB group.Compared with findings in Model rats,rats in Blood group exhibited improved mesenteric microcirculation associated with increased mesenteric blood flow and a larger arteriole diameter.Moreover,compared with findings in Model rats,Qi and QB rats exhibited increased left ventricular±dp/dtmax,decreased serum CKMB,Hcy,ET-1 levels,and reduced myocardial ultrastructural damage.CONCLUSION:Myocardial ischemia damage was suppressed by Traditional Chinese Medicines that regulate Qi and promote blood circulation.展开更多
Objective:Cluster needling at scalp acupoints has showed satisfying effects with acute cerebral ischemia in clinic whereas the mechanisms are not yet clear completely.This study investigated the influence of cluster n...Objective:Cluster needling at scalp acupoints has showed satisfying effects with acute cerebral ischemia in clinic whereas the mechanisms are not yet clear completely.This study investigated the influence of cluster needling at scalp acupoints on neurological function,as well as on neurofilament protein 200(NF200)and signal transducer and activator of transcription 3(STAT3)expression,in rats with acute cerebral ischemia.Methods:Fifty-four Sprague-Dawley rats were randomly assigned in equal numbers to the false operation(group F),model(group M),or cluster needling scalp acupuncture(group C)groups.Each group was divided into three subgroups,of six rats each,by acupuncture treatment time(24 h,7 days,and 14 days).The rat local cerebral ischemia model was prepared using a modified suture occlusion method.Group C rats were treated by cluster needling scalp acupuncture,while groups F and M did not receive acupuncture treatment.Neurological effects were evaluated using the Longa score.NF200 and STAT3 expression were measured by western blotting.Results:At 24 h,there were no statistical difference between group C and group M in nerve function(P>.05).On days 7 and 14,nerve function scores in group C were significantly lower than that in group M(respectively were P<.05 and P<.01).In addition,on days 14,expression of NF200 was significantly higher in group C compared with group M(P<.05).Compared with group M,STAT3 expression was also higher in group C on days 7 and 14,although these differences were not statistically significant(both P>.05).Conclusion:Cluster needling scalp acupuncture were efficient in improving nerve function scores in rats with cerebral ischemia,and promoting the recovery of motor function.These improvements were associated with increases in NF200 and STAT3 expression.展开更多
文摘Spinal cord ischemia(SCI),a frequent complication following open and endovascular thoracoabdominal aortic aneurysm(TAAA)repair,is a feared complication with relevant impact on a patient's quality of life.In the early days of open TAAA repair,more than one third of the patients suffered from SCI.Nowadays,due to improved preventive measures and the option of staged endovascular TAAA repair,10%of all patients are affected by spinal cord problems after TAAA repair(Rocha et al.,2020).
文摘背景:激素性股骨头缺血坏死的发病机制尚不明确,可能与内质网应激有关,控制内质网应激信号通路可能调控细胞的自噬与凋亡,对该病具有一定的防治作用。目的:通过探讨内质网应激与激素引起的细胞自噬、细胞凋亡的相互关系,总结内质网应激在激素性股骨头缺血坏死发病机制中的研究进展。方法:检索2000至2020年相关文献,以“内质网应激,股骨头坏死,未折叠蛋白反应,糖皮质激素,自噬,凋亡,缺血”为中文检索词检索CNKI、万方、维普数据库;以“endoplasmic reticulum stress,femur head necrosis,unfolded protein response,glucocorticoid,autophagy,apoptosis,ischaemia”为英文检索词检索PubMed、Web of science数据库。排除重复和较陈旧的文献及Meta分析,共81篇文献符合纳入标准。结果与结论:①未折叠蛋白反应为缓解内质网应激引发的3条下游信号通路可使细胞发生自噬和凋亡;②内质网应激与激素诱导的细胞自噬和凋亡及股骨头缺血有密切联系;③内质网应激可能是激素性股骨头缺血坏死发生过程中的病理环节,激素通过让细胞缺血缺氧激发内质网应激进而诱导细胞的自噬与凋亡,最终导致股骨头坏死。
基金This work was supported by the National Research Foundation of Korea(NRF)grants funded by the Korea government(MSIT,Ministry of Science and ICT)(NRF-2018M3A9E8023853(to JYC)NRF-2018R1C1B6006145(to JYC)NRF-2018R1A2A1A05020292(to BGK)and NRF-2019R1A5A2026045(to JYC and BGK).
文摘Subcortical ischemic white matter injury(SIWMI),pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging,is a common cause of cognitive decline in elderly.Despite its high prevalence,it remains unknown how various components of the white matter degenerate in response to chronic ischemia.This incomplete knowledge is in part due to a lack of adequate animal model.The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components.The SIWMI animal models are categorized into 1)chemically induced SIWMI models,2)vascular occlusive SIWMI models,and 3)SIWMI models with comorbid vascular risk factors.Chemically induced models display consistent lesions in predetermined areas of the white matter,but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities.Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified.When combined with comorbid vascular risk factors(specifically hypertension),however,they can produce progressive and definitive white matter lesions including diffuse rarefaction,demyelination,loss of oligodendrocytes,and glial activation,which are by far the closest to those found in human white matter hyperintensities lesions.However,considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models.In the meantime,in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury.Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities.
基金supported by the National Natural Science Foundation of China,No.81201513 (to QG)。
文摘Extremely low frequency electromagnetic fields(ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly understood.In this study, we established rat models of middle cerebral artery occlusion/reperfusion.One day after modeling, a group of rats were treated with ELF-EMF(50 Hz, 1 mT) for 2 hours daily on 28 successive days.Our results showed that rats treated with ELF-EMF required shorter swimming distances and latencies in the Morris water maze test than those of untreated rats.The number of times the platform was crossed and the time spent in the target quadrant were greater than those of untreated rats.The number of BrdU~+/NeuN~+ cells, representing newly born neurons, in the hippocampal subgranular zone increased more in the treated than in untreated rats.Up-regulation in the expressions of Notch1, Hes1, and Hes5 proteins, which are the key factors of the Notch signaling pathway, was greatest in the treated rats.These findings suggest that ELF-EMF can enhance hippocampal neurogenesis of rats with cerebral ischemia, possibly by affecting the Notch signaling pathway.The study was approved by the Institutional Ethics Committee of Sichuan University, China(approval No.2019255A) on March 5, 2019.
基金supported by a grant from the Forschungskommission der Medizinischen Fakult?t, Albert-Ludwigs-Universit?t Freiburg(SCHI1123/17, to MAS)。
文摘Infusion of the colloid hydroxyethylstarch has been used for volume substitution to maintain hemodynamics and microcirculation after e.g., severe blood loss.In the last decade it was revealed that hydroxyethylstarch can aggravate acute kidney injury, especially in septic patients.Because of the serious risk for critically ill patients, the administration of hydroxyethylstarch was restricted for clinical use.Animal studies and recently published in vitro experiments showed that hydroxyethylstarch might exert protective effects on the blood-brain barrier.Since the prevention of blood-brain barrier disruption was shown to go along with the reduction of brain damage after several kinds of insults, we revisit the topic hydroxyethylstarch and discuss a possible niche for the application of hydroxyethylstarch in acute brain injury treatment.
基金supported by the Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland(to RP)。
文摘Neurodegeneration in the brain after ischemia with reperfusion mimicking the neuropathology of Alzheimer's disease:Brain ischemia with reperfusion,which is one of the main causes of morbidity and mortality in the world,triggers various neuropathological changes characteristic for Alzheimer's disease(AD)such as increased blood-brain barrier permeability,excitotoxicity,necrosis,autophagy,mitophagy,apoptosis,neuroinflammation,amyloid plaques,neurofibrillary tangles,cerebral vessel pathology,and brain atrophy that lead to the death of neurons,deteriorating motor,sensory and cognitive functions(Figure 1)(Kato et al.,1988;Wisniewski et al.,1995;Van Groen et al.,2005;Kocki et al.,2015;Ułamek-Koziołet al.,2016,2017,2019).Brain ischemia is recognized as a major contributor to the dysfunction of an aging brain and the development of neurodegenerative diseases,including AD(Pluta,2019).
基金This study was funded by the National Natural Science Foundation of China,No.81470200(to XJR).
文摘Electroacupuncture(EA)has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia.However,there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects.In this study,EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed.Except for the normal group,rats in other groups were fed a high-fat diet throughout the whole experiment.Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks.Middle cerebral artery thrombus models were induced by pasting 50%FeCl3 filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group.EA1 group rats received EA at bilateral ST40(Fenglong)for 7 days before the thrombosis.Rats in the EA1 and EA2 groups received EA at GV20(Baihui)and bilateral ST40 for 14 days after model establishment.Neuronal health was assessed by hematoxylin-eosin staining in the brain.Hyperlipidemia was assessed by biochemical methods that measured total cholesterol,triglyceride,low-density lipoprotein and high-density lipoprotein in blood sera.Behavioral analysis was used to confirm the establishment of the model.Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region.The results demonstrated that,compared with the model group,blood lipid levels significantly decreased,glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups.The repair effect was superior in the EA1 group than in the EA2 group.These findings confirm that EA can reduce blood lipid,inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after
基金supported by the National Natural Science Foundation of China,Nos.81771271(to JF),81902537(to MJY),82001475(to SJY)a Scientific Fund of Shengjing Hospital of China Medical University,No.M0124(to SJY)+1 种基金the“345 Talent Project”from Shengjing Hospital of China Medical University(to SJY)the Natural Science Foundation of Liaoning Province of China,No.20180550913(to MJY).
文摘Apoptosis is an important programmed cell death process involved in ischemia/reperfusion injury.MicroRNAs are considered to play an important role in the molecular mechanism underlying the regulation of cerebral ischemia and reperfusion injury.However,whether miR-670 can regulate cell growth and death in cerebral ischemia/reperfusion and the underlying mechanism are poorly understood.In this study,we established mouse models of transient middle artery occlusion and Neuro 2a cell models of oxygen-glucose deprivation and reoxygenation to investigate the potential molecular mechanism by which miR-670 exhibits its effects during cerebral ischemia/reperfusion injury both in vitro and in vivo.Our results showed that after ischemia/reperfusion injury,miR-670 expression was obviously increased.After miR-670 expression was inhibited with an miR-670 antagomir,cerebral ischemia/reperfusion injury-induced neuronal death was obviously reduced.When miR-670 overexpression was induced by an miR-670 agomir,neuronal apoptosis was increased.In addition,we also found that miR-670 could promote Yap degradation via phosphorylation and worsen neuronal apoptosis and neurological deficits.Inhibition of miR-670 reduced neurological impairments after cerebral ischemia/reperfusion injury.These results suggest that microRNA-670 aggravates cerebral ischemia/reperfusion injury through the Yap pathway,which may be a potential target for treatment of cerebral ischemia/reperfusion injury.The present study was approved by the Institutional Animal Care and Use Committee of China Medical University on February 27,2017(IRB No.2017PS035K).
基金supported by the Brazilian National Council for Scientific Research。
文摘The discovery that new neurons are produced in some regions of the adult mammalian brain is a paradigm-shift in neuroscience research.These new-born cells are produced from neuroprogenitors mainly in the subventricular zone at the margin of the lateral ventricle,subgranular zone in the hippocampal dentate gyrus and in the striatum,a component of the basal ganglia,even in humans.In the human hippocampus,neuroblasts are produced even in elderlies.The regulation of adult neurogenesis is a complex phenomenon involving a multitude of molecules,neurotransmitters and soluble factors released by different sources including glial cells.Microglia,the resident macrophages of the central nervous system,are considered to play an important role on the regulation of adult neurogenesis both in physiological and pathological conditions.Following stroke and other acute neural disorders,there is an increase in the numbers of neuroblast production in the neurogenic niches.Microglial activation is believed to display both beneficial and detrimental role on adult neurogenesis after stroke,depending on the activation level and brain location.In this article,we review the scientific evidence addressing the role of microglial activation on adult neurogenesis after ischemia.A comprehensive understanding of the microglial role after stroke and other neural disorders it is an important step for development of future therapies based on manipulation of adult neurogenesis.
文摘<strong>Objectives:</strong> To identify the main risk factors of vascular cognitive impairment in patients with acute cerebral infarction by Meta-analysis, and provide references for the effective prevention of the cognitive impairment in stroke patients. <strong>Methods:</strong> To retrieve the observational research literatures that refer to the risk factors of vascular cognitive impairment in patients with ischemic stroke, which are published on China National Knowledge Infrastructure (CNKI), Wanfang and Weipu Chinese databases. The screening and data extraction of these literatures are independently completed by two researchers, who also give the quality evaluation of the literatures according to the evaluation criterion of the Australian JBI Evidence-Based Health Care Center. Then, Meta-analysis is conducted by using Revman5.3 software. <strong>Results:</strong> There are twenty-eight articles selected from 1507 literatures, with a total of 10,711 cases and 50 risk factors included. Among them, there are combined effects of ten factors which have statistical significance, such as infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetes mellitus, age, history of cerebral infarction, hyperlipoidemia and education level. The relational merging OR value and 95% CI between the type-variable factors and cognitive impairment are 3.25 (1.84, 5.76);2.98 (2.58, 3.45);2.79 (1.69, 4.59);2.35 (1.93, 2.85);2.25 (1.86, 2.71);2.14 (2.10, 2.18);1.82 (1.62, 2.03);1.54 (1.24, 1.92);1.45 (1.34, 1.56);0.83 (0.78, 0.89). <strong>Conclusion: </strong>Infarction area, alcohol consumption, smoking, hyper homocysteinemia, hypertension, diabetesmellitus, age, history of cerebral infarction, hyperlipoidemia and low education level are the main risk factors for vascular cognitive impairment in patients with acute cerebral infarction. Clinical nursing staff should include it into the routine assessment of patients with acute cerebral infarction and actively prevent and intervene.
文摘<strong>Background:</strong> <span style="font-family:""><span style="font-family:Verdana;">Beta-thalassemia is a hereditary haemoglobinopathy caused by defective hemoglobin (Hb) </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-globin synthesis, leading to excess </span><i><span style="font-family:Verdana;">α</span></i><span style="font-family:Verdana;">-globin chains that cause hemolysis and impair erythropoiesis. Ischemia modified albumin (IMA) is not a signal protein and not generated in pro-inflammatory state alone but rather an end product of oxidative stress.</span><b><span style="font-family:Verdana;"> Objectives: </span></b><span style="font-family:Verdana;">The aim of the study was to evaluate ischemia modified albumin (IMA) and C-reactive protein (CRP) in children with </span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-thalassemia major and its relation to different iron chelators. </span><b><span style="font-family:Verdana;">Patients and Methods: </span></b><span style="font-family:Verdana;">The study was carried on 40 children diagnosed as beta-thalassemia major recruited from the outpatient clinic and the pediatric department, at Al-Zahraa University Hospital, Faculty of medicine for Girls, Al-Azhar University and EL Minia Insurance Hospital. They were 20 male and 20 female, aged from 4 - 11 years. Another 40 apparently healthy children age and sex matched as control group. CRP and IMA were determined for all participants.</span><b><span style="font-family:Verdana;"> Results:</span></b><span style="font-family:Verdana;"> There were significant increases in serum CRP, IMA and ferritin levels in patients group compared to control group. There were significant decreases of IMA and CRP levels of thalassemic patients on chelation deferiprone (DFP) compared to deferasirox (DFX) P-value (<0.01) for each. There was a significant positive correlation between serum ferritin and both CRP and IMA levels in thalassemic childr
基金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Wuhan Tongji Hospital,No.2017A002Wuhan Science and Technology Bureau,No.2017060201010181.
文摘BACKGROUND The prognosis of acute mesenteric ischemia(AMI)caused by superior mesenteric venous thrombosis(SMVT)remains undetermined and early detection of transmural bowel infarction(TBI)is crucial.The predisposition to develop TBI is of clinical concern,which can lead to fatal sepsis with hemodynamic instability and multi-organ failure.Early resection of necrotic bowel could improve the prognosis of AMI,however,accurate prediction of TBI remains a challenge for clinicians.When determining the eligibility for explorative laparotomy,the underlying risk factors for bowel infarction should be fully evaluated.AIM To develop and externally validate a nomogram for prediction of TBI in patients with acute SMVT.METHODS Consecutive data from 207 acute SMVT patients at the Wuhan Tongji Hospital and 89 patients at the Guangzhou Nanfang Hospital between July 2005 and December 2018 were included in this study.They were grouped as training and external validation cohort.The 207 cases(training cohort)from Tongji Hospital were divided into TBI and reversible intestinal ischemia groups based on the final therapeutic outcomes.Univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for TBI using the training data,and a nomogram was subsequently developed.The performance of the nomogram was evaluated with respect to discrimination,calibration,and clinical usefulness in the training and external validation cohort.RESULTS Univariate and multivariate logistic regression analyses identified the following independent prognostic factors associated with TBI in the training cohort:The decreased bowel wall enhancement(OR=6.37,P<0.001),rebound tenderness(OR=7.14,P<0.001),serum lactate levels>2 mmol/L(OR=3.14,P=0.009)and previous history of deep venous thrombosis(OR=6.37,P<0.001).Incorporating these four factors,the nomogram achieved good calibration in the training set[area under the receiver operator characteristic curve(AUC)0.860;95%CI:0.771-0.925]and the external validation set(AUC 0.851
基金Supported by National key basic research and development plan(973 Program)(No.2015CB554405,2015CB554402)。
文摘OBJECTIVE:To investigate the efficacy of Chinese medicines on Qi stagnation and blood stasis in rats with myocardial ischemia.METHODS:Fifty male Wistar rats were randomly divided into five groups(n=10)as follows:(a)sham operation(Sham),(b)myocardial ischemia(Model),(c)treatment that regulates Qi(Qi),(d)treatment that promotes blood circulation(Blood),(e)treatment that both regulates Qi and promotes blood circulation(QB).The rat model was established via activities restriction for 6 h followed by tail clamp stimulation for 5 mins every day for 7 d and occlusion left coronary anterior descending artery.Afterwards rats were treated with medicines that regulate Qi and/or promote blood circulation via gavage for 14 d.Behavioral parameters were evaluated using open field and elevated plus-maze tests.The tongue color and sublingual vein were visually examined.Blood flow perfusion of tongue and auricle were detected using PIMⅡ.The mesenteric microcirculation was examined via capillaroscopy,and hemodynamics was assessed using a polygraph system.Serum homocysteine(Hcy),creatine kinase isoenzyme(CKMB)levels and endothelin-1(ET-1)were measured.Hematoxylin and eosin staining and transmission electron microscopy were employed to detect the myocardial morphology and ultrastructure,respectively.RESULTS:Compared with findings in Sham group,rats in model group had coarse hair,dark mucosa of the lips and claw,low activity,and increased anxiety.Compared with findings in Model group,rats in the three treatment groups exhibited a lighter tongue color without an extended and varicose sublingual vein.There were significant increases of auricle blood flow perfusion in the Qi group and tongue bottom blood flow perfusion in the QB group.Compared with findings in Model rats,rats in Blood group exhibited improved mesenteric microcirculation associated with increased mesenteric blood flow and a larger arteriole diameter.Moreover,compared with findings in Model rats,Qi and QB rats exhibited increased left ventricular±dp/dtmax,decreased serum CKMB,Hcy,ET-1 levels,and reduced myocardial ultrastructural damage.CONCLUSION:Myocardial ischemia damage was suppressed by Traditional Chinese Medicines that regulate Qi and promote blood circulation.
基金This study was supported by grants from the National Natural Science Foundation of China(grant No.81473775).
文摘Objective:Cluster needling at scalp acupoints has showed satisfying effects with acute cerebral ischemia in clinic whereas the mechanisms are not yet clear completely.This study investigated the influence of cluster needling at scalp acupoints on neurological function,as well as on neurofilament protein 200(NF200)and signal transducer and activator of transcription 3(STAT3)expression,in rats with acute cerebral ischemia.Methods:Fifty-four Sprague-Dawley rats were randomly assigned in equal numbers to the false operation(group F),model(group M),or cluster needling scalp acupuncture(group C)groups.Each group was divided into three subgroups,of six rats each,by acupuncture treatment time(24 h,7 days,and 14 days).The rat local cerebral ischemia model was prepared using a modified suture occlusion method.Group C rats were treated by cluster needling scalp acupuncture,while groups F and M did not receive acupuncture treatment.Neurological effects were evaluated using the Longa score.NF200 and STAT3 expression were measured by western blotting.Results:At 24 h,there were no statistical difference between group C and group M in nerve function(P>.05).On days 7 and 14,nerve function scores in group C were significantly lower than that in group M(respectively were P<.05 and P<.01).In addition,on days 14,expression of NF200 was significantly higher in group C compared with group M(P<.05).Compared with group M,STAT3 expression was also higher in group C on days 7 and 14,although these differences were not statistically significant(both P>.05).Conclusion:Cluster needling scalp acupuncture were efficient in improving nerve function scores in rats with cerebral ischemia,and promoting the recovery of motor function.These improvements were associated with increases in NF200 and STAT3 expression.