Electroacupuncture improves learning and memory functions in a rat cerebral ischemia/reperfusion injury model through PI3K/Akt signaling pathway activation

Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase(PI3 K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3 K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting(GV24) and Baihui(GV20) acupoints, with a dilatational wave(1–20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3 K/Akt signaling pathwayrelated factors Beclin-1, mammalian target of rapamycin(mTOR), and PI3 K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3 K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting(GV24) and Baihui(GV20) acupoints activated the PI3 K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China(approval No. 8150150901) on March 10, 2016.     

Physiopathology of ischemic stroke and its modulation using memantine:evidence from preclinical stroke

Ischemic stroke is the most common type of cerebrovascular disease and is caused by an interruption of blood flow in the brain.In this disease,two different damage areas are identifying:the lesion core,in which cells quickly die;and the penumbra(surrounding the lesion core),in which cells are functionally weakened but may recover and restore their functions.The currently approved treatments for ischemic stroke are the recombinant tissue plasminogen activator and endovascular thrombectomy,but they have a short therapeutic window(4.5 and 6 hours after stroke onset,respectively)and a low percentage of stroke patients actually receive these treatments.Memantine is an approved drug for the treatment of Alzheimer's disease.Memantine is a noncompetitive,low affinity and use-dependent antagonist of N-methyl-D-aspartate glutamate receptor.Memantine has several advantages over developing a new drug to treat focal ischemic stroke,but the most important is that it has sufficient safe probes in preclinical models and humans,and if the preclinical studies provide more evidence about pharmacological actions in tissue protection and repair,this could help to increase the number of clinical trials.The present review summarizes the physiopathology of isquemic stroke and the pharmacological actions in neuroprotection and neuroplasticity of memantine in the post stroke stage of preclinical stroke models,to illustrate their potential to improve functional recovery in human patients.     

急性缺血性脑卒中CISS分型与危险因素相关性分析

目的探讨急性缺血性卒中中国缺血性卒中亚型（CISS）分型与不同危险因素的关系。方法回顾性分析连续登记的急性缺血性脑梗死患者,记录其危险因素,并按CISS分型标准将急性缺血性卒中分为5种类型并分析相关因素对其发生风险的影响。结果在纳入标准的212例急性缺血性卒中患者中,大动脉粥样硬化型99例（46.7%）、心源性卒中型35例（16.5%）、穿支动脉疾病45例（21.2%）、其他病因型5例（2.4%）、病因不确定型28例（13.2%）。吸烟者、高血压病、冠心病、心房颤动者在5亚型间比例差异具有统计学意义（P〈0.05）。相关和回归分析显示冠心病、心房颤动与心源性卒中亚型有正相关性（β=1.34、2.206,P〈0.05）,高血压病与穿支动脉疾病亚型有相关性,为正相关性（β=1.074,P〈0.05）。结论不同类型缺血性脑卒中与不同的危险因素有关,心房颤动、冠心病是心源性卒中亚型的危险因素,高血压病是穿支动脉疾病亚型的危险因素。     

急性冠状动脉综合征并缺血性脑卒中与血清细胞因子的关系

目的分析急性冠状动脉综合征合并缺血性脑卒中的临床治疗效果。方法选取2012-03—2013-05我院诊治的120例伴缺血性脑卒中急性冠状动脉综合征患者,均在药物治疗前12h及药物治疗2个疗程后,空腹采集静脉血检测细胞因子,观察治疗前后血清细胞因子的变化,观察临床治疗效果。结果药物治疗后,血清细胞因子IL-18、hs-CRP、干扰素-γ等细胞因子的水平产生显著变化,治疗前后的细胞因子水平有显著性差异(P0.05),总有效率94.2%。结论通过药物治疗,显著改变了伴缺血性脑卒中急性冠状动脉综合征患者的细胞因子水平,获得较好的临床效果,值得临床推广使用。     

首次脑梗死患者和正常健康者血清超敏C-反应蛋白的性别差异及其意义

目的探讨首次脑梗死患者与正常健康体检者血清超敏C-反应蛋白(hsCRP)的性别差异及意义。方法选取1 3 8例首次脑梗死患者(NIHSS评分<5分)作为脑梗死组,将其分为男性组和女性组。选取1 5 0例健康体检者作为正常组,亦分为男性组和女性组。检测各组患者血清hsCRP水平。结果脑梗死组血清hsCRP水平明显高于正常组(P<0.05)。男性脑梗死组与女性脑梗死组血清hsCRP相比较差异无统计学意义(P>0.0 5)。男性正常组与女性正常组血清hsCRP相比较,男性组高于女性组,差异有统计学意义(P<0.0 5)。男性脑梗死组与男性正常组血清hsCRP相比较差异无统计学意义(P>0.0 5)。女性脑梗死组与女性正常组血清hsCRP相比较差异有统计学意义(P<0.0 5)。结论血清hsCRP水平存在性别差异。炎症反应与女性脑梗死的发病可能有着更为密切的联系。     

青年缺血性脑卒中患者病因及相关危险因素分析

目的探讨青年缺血性卒中患者病因及危险因素。方法收集71例青年缺血卒中患者及80例中老年缺血性卒中患者的临床资料,同时选取140例青年健康体检自然人群作为对照,进行病因及相关危险因素分析。结果青年缺血组TOAST病因分型按比例依次为大动脉粥样硬化型（LAA）40.8%、小动脉闭塞型（SAO）28.2%、不明原因型（UND）15.5%、其它原因型（OTH）9.9%、心源性栓塞型（CE）5.6%。与中老年缺血组比较,其UND型比例明显增高（P〈0.05）。青年缺血性脑卒中易患因素依次为吸烟、高脂血症、高血压病、糖尿病、心脏病。与中老年缺血性组相比,青年缺血组中男性患者比例显著增高（P〈0.05）。结论青年缺血性卒中以LAA型最常见;其发病为多因素共同作用结果。     

P2X7 receptor activation aggravates NADPH oxidase 2-induced oxidative stress after intracerebral hemorrhage

Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor(P2X7R), which is activated by the abnormal accumulation of extracellular ATP, plays an important role in the regulation of oxidative stress in the central nervous system, although the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage remain unclear. Mouse models of intracerebral hemorrhage were established through the stereotactic injection of 0.075 U VII collagenase into the right basal ganglia. The results revealed that P2X7R expression peaked 24 hours after intracerebral hemorrhage, and P2X7R expressed primarily in neurons. The inhibition of P2X7R, using A438079(100 mg/kg, intraperitoneal), reduced nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2) expression and malondialdehyde generation, increased superoxide dismutase and glutathione/oxidized glutathione levels, and alleviated neurological damage, brain edema, and apoptosis after intracellular hemorrhage. The P2X7R inhibitor A438079(100 mg/kg, intraperitoneal injection) inhibited the activation of extracellular signal-regulated kinase 1/2(ERK1/2) and nuclear factor kappa-B(NF-κB) after intracerebral hemorrhage. Blocking ERK1/2 activation, using the ERK1/2 inhibitor U0126(2 μg, intraventricular injection), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation after intracellular hemorrhage. Similarly, the inhibition of NF-κB, using the NF-κB inhibitor JSH-23(3.5 μg, intraventricular), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation. Finally, GSK2795039(100 mg/kg, intraperitoneal), a NOX2 antagonist, attenuated P2X7R-mediated oxidative stress, neurological damage, and brain edema after intracerebral hemorrhage. The results indicated that P2X7R activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways following intracerebral hemorrhage in mice. The present study was approved by the Ethics Committee of Huazhong University of Science and Technology, China(approval No. TJ-A20160805) on August 26, 2016.     

移动卒中单元在院前救治急性缺血性脑卒中的应用

急性缺血性脑卒中是严重威胁人类健康的疾病,时间窗内的治疗对该病至关重要。传统模式往往由于院前时间的延误以及入院后头颅CT检查时间的延误,使患者错过了最佳的治疗时间。移动卒中单元的出现使救治时间大大缩短,患者在配备头颅CT的急救车上即可进行诊治,为院内的下一步治疗节约了时间,提高了急性脑卒中患者的救治率,降低了致残率。     

老年急性缺血性脑卒中患者颈动脉斑块检出率及其与脑卒中复发的相关性

目的 应用多普勒彩色超声诊断仪评估老年急性缺血性脑卒中（AIS）患者颈动脉斑块检出情况,总结斑块发生的高危因素,并分析其与AIS复发的相关性。方法 以2020年1月至2020年6月于常州市第一人民医院神经内科和老年医学科住院的首次发生AIS,并且72 h内入院的老年患者236例为研究对象。依据颈动脉超声检查结果分为颈动脉斑块组（199例）和无颈动脉斑块组（37例）。收集并分析2组患者的临床资料及随访1.5年后脑卒中复发情况。结果 老年AIS患者颈动脉斑块检出率为84.3%。60~69岁、70~79岁及≥80岁患者颈动脉斑块检出率分别为74.7%、86.9%、96.0%,随着年龄增长颈动脉斑块检出率逐渐增加。颈动脉斑块组女性、高血压史和糖尿病史的比例明显高于无斑块组（均P<0.05）。颈动脉斑块组与无颈动脉斑块组脑卒中复发事件发生率比较,差异有统计学意义（P<0.05）。多因素Logistic回归分析结果显示,年龄（OR=1.070,95%CI：1.02~1.122,P=0.005）、糖尿病史（OR=2.262,95%CI：1.055~4.850,P=0.036）、颈动脉斑块（OR=8.128,95%CI：1.077~61.348,P=0.042）是AIS复发的独立影响因素。结论 老年AIS患者颈动脉斑块检出率高。年龄、性别、高血压史、糖尿病史是颈动脉粥样硬化的危险因素。年龄、糖尿病史、颈动脉斑块与脑卒中复发事件发生相关。     

进展性缺血性脑卒中危险因素分析及微栓子对卒中进展的预测价值

目的探讨进展性缺血性脑卒中(PIS)患者的危险因素及微栓子对进展性卒中的预测价值。方法纳入2016年3月至2018年3月就诊于内蒙古自治区人民医院神经内科的50例PIS患者及同时期非进展的缺血性卒中病人62例,所有纳入的患者均行头颅磁共振、颈动脉血管超声、心脏彩超、心电图、48 h内微栓子检查,并对纳入的患者进行问卷调查。结果微栓子阳性PIS患者病灶多位于皮质(P0.05)。PIS与微栓子、低密度脂蛋白异常、院前未服用阿司匹林、院前服用降压药物、颈动脉斑块等因素显著相关(P 0.05)。logistic回归分析提示微栓子(OR=7.246,P=0.001)、低密度脂蛋白异常(OR=3.879,P=0.007)、颈动脉斑块(OR=4.177,P=0.007)、院前未口服阿司匹林(OR=4.304,P=0.046)、院前服用降压药物(OR=3.734,P=0.01)为PIS的独立危险因素。结论微栓子、低密度脂蛋白异常、院前未口服阿司匹林、院前服用降压药物、颈动脉斑块是PIS危险因素,且微栓子更具预测价值。     

进展性缺血性脑卒中危险因素分析及微栓子对卒中进展的预测价值

目的 探讨进展性缺血性脑卒中（PIS）患者的危险因素及微栓子对进展性卒中的预测价值。方法 纳入2016年3月至2018年3月就诊于内蒙古自治区人民医院神经内科的50例PIS患者及同时期非进展的缺血性卒中病人62例,所有纳入的患者均行头颅磁共振、颈动脉血管超声、心脏彩超、心电图、48 h内微栓子检查,并对纳入的患者进行问卷调查。结果 微栓子阳性PIS患者病灶多位于皮质（P<0.05）。PIS与微栓子、低密度脂蛋白异常、院前未服用阿司匹林、院前服用降压药物、颈动脉斑块等因素显著相关（P<0.05）。logistic回归分析提示微栓子（OR=7.246,P=0.001）、低密度脂蛋白异常（OR=3.879,P=0.007）、颈动脉斑块（OR=4.177,P=0.007）、院前未口服阿司匹林（OR=4.304,P=0.046）、院前服用降压药物（OR=3.734,P=0.01）为PIS的独立危险因素。结论 微栓子、低密度脂蛋白异常、院前未口服阿司匹林、院前服用降压药物、颈动脉斑块是PIS危险因素,且微栓子更具预测价值。     

Wide-range C-reactive protein efficacy in acute ischemic stroke patients

OBJECTIVE: To compare the recently introduced wide-range C-reactive protein (wr-CRP) with the widely used high-sensitivity Behring Dade method (hs-CRP) in acute stroke/transient ischemic attack (TIA) patients. MATERIALS AND METHODS: A total of 119 consecutive patients admitted to a tertiary medical center with acute ischemic stroke/TIA were included in the study. Venous blood was obtained for both assays during the first 24 h, 3-5 days, as well as 3-6 months thereafter. RESULTS: A highly significant correlation (r=0.994, P<0.0001) was found between the two methods even when analyzed at three different time points. In addition, a similar correlation was noted between these two assays and other commonly used biomarkers, including white blood cell count, Westergren's sedimentation rate and quantitative fibrinogen. CONCLUSION: Real-time, on-line and low-cost wr-CRP assay is a reasonable alternative to the Behring Dade hs-CRP method in acute stroke/TIA patients.     

急性脑梗死后出血转化诊断与处理

急性脑梗死后出血转化与脑梗死预后不良相关,也是溶栓等疗法使用不足的重要原因。为更好地认识和处理脑梗死后出血转化,提高再灌注等循证疗法的使用率,临床医生有必要了解当前国内外公认的出血转化定义、分类分型、诊断和处理原则。出血转化处理总原则与自发性脑出血类似,但其特殊性问题值得注意,例如,不同药物所致出血的处理及拮抗剂使用,抗栓疗法的停药与重启使用时间等问题。同时也应认识到,很多问题缺乏研究证据需要进一步研究。     

血尿酸水平与缺血性脑卒中的相关性

目的探讨血尿酸水平与缺血性脑卒中之间的相关性。方法采用病例对照研究,选择2006-07—2011-03在我院神经内科住院的缺血性脑卒中患者177例（病例组）;对照组202例,为同期我院健康体检者。对所有纳入对象测定禁食12h后静脉血清尿酸值及其他生物化学指标,探讨血尿酸水平与缺血性脑卒中的关系。结果病例组血清尿酸水平（359.47±70.84）μmol/L显著高于对照组（310.26±76.35）μmol/L,2组比较差异有统计学意义（P〈0.01）。多因素Logistic回归分析显示,糖尿病、高血压、LDL-C及血尿酸是缺血性脑卒中发生的独立危险因素,血尿酸水平升高与缺血性脑卒中密切相关（OR=1.183,95%CI1.052～1.331;P=0.018）。结论缺血性脑卒中患者血尿酸水平显著升高,血尿酸与缺血性脑卒中发生密切相关,可能是其独立危险因素。     

Profile and associations of central pulse wave velocity and central pulse pressure among ischemic stroke patients

Arterial stiffness, a known risk factor for atherosclerosis, can be measured directly with carotid–femoral pulse wave velocity (CPWV) and indirectly with central pulse pressure (CPP). We aimed to compare central and brachial pulse pressures, and to profile CPWV and CPP among ischemic stroke patients. We studied 198 consecutive prospective ethnic Chinese and South Asian ischemic stroke patients, measuring brachial pressures, central pressures and CPWV under standardized conditions using established methods. The mean CPWV was 11.6 ± 3.2 m/s and CPP was 64 ± 28 mmHg. CPP was significantly lower than brachial pulse pressure. CPWV and CPP were both independently associated with older age and hypertension. Among ischemic stroke patients, brachial pulse pressure cannot be used as a surrogate for CPP. Older age and hypertension are associated with arterial stiffening.     

Hurdles in stroke thrombolysis: Experience from 100 consecutive ischemic stroke patients

Background:

Acute management of ischemic stroke involves thrombolysis within 4.5 h. For a successful outcome, early recognition of stroke, transportation to the hospital emergency department immediately after stroke, timely imaging, proper diagnosis, and thrombolysis within 4.5 h is of paramount importance.

Aim:

To analyze the obstacles for thrombolysis in acute stroke patients.

Materials and Methods:

The study was conducted in a tertiary care center in South India. A total of hundred consecutive patients of acute ischemic stroke who were not thrombolysed, but otherwise fulfilled the criteria for thrombolysis were evaluated prospectively for various factors that prevented thrombolysis. The constraints to thrombolysis were categorized into: i) Failure of patient to recognize stroke symptoms, ii) patient''s awareness of thrombolysis as a treatment modality for stroke, iii) failure of patient''s relative to recognize stroke, iv) failure of primary care physician to recognize stroke, v) transport delays, vi) lack of neuroimaging and thrombolysis facility, and vii) nonaffordability.

Results:

The biggest hurdle for early hospital presentation is failure of patients to recognize stroke (73%), followed by lack of neuroimaging facility (58%), nonaffordability (56%), failure of patient''s relative to recognize stroke (38%), failure of the primary care physician to recognize stroke (21%), and transport problems (13%). Awareness of thrombolysis as a treatment modality for stroke was seen only in 2%.

Conclusion:

Considering the urgency of therapeutic measures in acute stroke, there is necessity and room for improvement to overcome various hurdles that prevent thrombolysis.     

nsulin resistance and occurrence and prognosis of schemic stroke——A non-randomized concurrent control and intra-group comparison

BACKGROUND： Clinical evidence has demonstrated that insulin resistance might be an independent risk factor for ischemic stroke, which has not been recognized. At present, insulin resistance has been proven to be an independent risk factor for coronary arteriosclerotic heart disease. However, the relationship between the onset and prognosis of ischemic stroke remains unclear. OBJECTIVE： This study was designed to analyze the relationship between insulin resistance and ischemic stroke and the correlation between insulin resistance and stroke risk factor, and to investigate the relationship between insulin resistance and ischemic stroke prognosis as well as whether insulin resistance is an independent prognostic factor. DESIGN： A non-randomized concurrent control experiment. SETTING： Department of Geriatric Disease, Second Affiliated Hospital of Kunming Medical College. PARTICIPANTS： A total of 106 inpatients with ischemic stroke of the cervical internal carotid artery, who had suffered from the disease within the previous 72 hours, were admitted to the Department of Neurology, First Affiliated Hospital of Kunming Medical College from March to December in 2005 and, recruited for the present study. All 106 inpatients corresponded to the diagnostic criteria of ischemic stroke, formulated at the Fourth National Cerebrovascular Disease Conference in 1995, and were confirmed as having had an ischemic stroke by CT/MRI examinations. The patient group consisted of 54 males and 52 females. An additional 50 healthy individuals, who received health examinations simultaneously, were included as controls. Among the control subjects, there were 26 males and 24 females. Informed consent for laboratory measurements was obtained from all subjects; this study was approved by the Hospital Ethics Committee. METHODS： Following admission, all subjects were inquired of age, gender, previous history, blood pressure, body temperature, admission time, and smoking habits. Meanwhile, they were scored on clinical neurological functi