B细胞调控动脉粥样硬化性卒中研究进展

动脉粥样硬化是缺血性卒中的主要病理学基础。近年研究发现,动脉第三淋巴器官富含B细胞,可通过局部免疫应答对动脉粥样硬化斑块的形成与进展发挥重要调节作用;其中部分B细胞调控因子可使梗死灶体积缩小,有望成为缺血性卒中治疗的替代性选择。本文拟对B细胞亚群参与调控动脉粥样硬化和缺血性卒中进展的作用与机制进行综述,以助于探寻动脉粥样硬化、缺血性卒中发生发展的免疫机制及免疫治疗潜能。     

染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的Meta分析

目的 缺血性卒中（ischaemic stroke,IS）是一种与遗传因素密切相关的多基因疾病。以单核苷酸多态性（single nucleotide polymorphism,SNP）为遗传标记系统的全基因组关联研究（Genomewide Association Studies,GWAS）发现染色体9p21多态性是血管粥样硬化的独立危险因素,与动脉粥样硬化性缺血性卒中易感风险相关;但由于样本量较小,通过比较等位基因频率分布,显示其在病例组与对照组之间无明显差异,这突出了更大规模研究的必要性。本研究拟对目前已发表的有关染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的病例-对照研究严格质量控制后进行Meta分析,旨在明确染色体9p21与动脉粥样硬化性缺血性卒中易感相关性的SNP种类,并对其与疾病发生风险的大小进行评估。方法 联合检索目前已发表的全部有关染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的病例-对照研究,制定严格的纳入排除质量控制标准,应用国际Cochrane系统评价协作网提供的Meta分析专用软件RevMan5.0对数据进行Meta分析,用森林图（Forest Plot）展示各个研究的OR（odds ratio）值及95％可信区间（confidence interval,CI）以及合并统计的OR值及95%CI,系统评价染色体9p21与动脉粥样硬化性缺血性卒中易感相关性的SNP在病例组与对照组分布有无差异,分析得到染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的统计学意义。结果 进入Meta分析的资料涉及6项跨越欧洲与北美洲的多中心临床病例-对照研究。进入Meta分析的基因多态性涉及染色体9p21上的7种SNP：rs7044859、rs496892、rs564398、rs7865618、rs1537378、rs2383207及rs10757278。其中,rs564398、rs7865618、rs1537378、rs2383207和rs10757278与动脉粥样硬化性缺血性卒中相关性具有统计学意义,与动脉粥样硬化性缺血性卒中易感风险相关。而rs7044859、rs496892与动脉粥样硬化性缺血性卒中相关性无统计学意义。结论 本研究发现染色体9p21的5种SNP（rs564398、rs7865618、rs1537378、rs2383207及rs10757278）与动脉粥样硬化性缺血性卒中具有易感相关性,染色体9p21变异被认为是血管粥样硬化的危险因素,是动脉粥样硬化性缺血性卒中的候选易感基因。     

IL-6和动脉粥样硬化性缺血性卒中的关系研究进展

缺血性卒中是一种病因复杂的综合征,其中动脉粥样硬化是主要病因之一。流行病学、分子生物学证据表明IL-6促进动脉粥样硬化斑块的形成和生长,影响缺血性卒中的发生、发展及预后。新近的临床研究进一步证实干预IL-6通路有望成为缺血性卒中治疗的新靶点。本综述从分子生物学、流行病学和新近开展的临床研究阐述IL-6在缺血性卒中发生、预后中的作用,以及作为潜在治疗靶点的可能性。     

缺血性脑卒中的CISS分型及危险因素分析

目的分析缺血性卒中CISS分型及其相关危险因素,为缺血性脑卒中的治疗及预防提供依据。方法前瞻性研究神经内科连续入院的缺血性脑卒中患者,进行CISS分型,研究缺血性卒中的相关危险因素。结果缺血性脑卒中可见于不同的CISS亚型,以颅内外大动脉粥样硬化最常见,高血压对大动脉粥样硬化及穿支动脉病变的发生有明显作用;糖尿病、血脂异常、高同型半胱氨酸血症与大动脉粥样硬化关系密切;心房纤颤对心源性脑卒中的发生有显著作用。结论不同亚型缺血性脑卒中的危险因素不同,临床的预防与治疗措施应有针对性。     

磁共振成像：评估动脉粥样硬化斑块的重要影像检查方法

缺血性卒中是中老年人常见病,致残率高、死亡率高。发生缺血性卒中的原因众多,约30%的缺血性卒中归因于颈动脉粥样硬化斑块;而颅内动脉粥样硬化在不同种族间的发生率存在差异,亚裔、拉丁裔及非洲裔人群中的发生率较高加索裔明显增高。对于我国人群的动脉粥样硬化流行病学调查资料显示:大于40岁的人群中约7%存在颅内动脉粥样硬化性狭窄;     

高分辨率磁共振成像评估大脑中动脉粥样硬化性狭窄研究进展

<正>颅内动脉粥样硬化性狭窄(intracranial atherosclerotic stenosis,ICAS)是缺血性脑卒中的主要发病机制之一,因大脑中动脉(middle cerebral artery,MCA)的供血区域广泛,且易发生粥样硬化性狭窄,其供血区域的缺血性卒中发生率高,严重威胁中国人群的健康~([1])。研究显示,颅内动脉粥样硬化易损斑块破裂是缺血性卒中发生的主要促进因素~([2])。目前临床治疗     

磁共振斑块成像与缺血性卒中的相关性研究进展

动脉粥样硬化易损斑块破裂是导致缺血性卒中的主要原因。与组织病理学对照研究证实,
高分辨率磁共振成像可以无创性评价动脉粥样硬化斑块的负荷、成分及其易损性。大量研究显示,
脑血管粥样硬化斑块的磁共振表现特征与缺血性卒中具有明显的相关性。本文将从磁共振斑块成
分特征与缺血性脑血管事件的相关性方面进行综述,为缺血性卒中的病因学诊断和疾病的预防提供
重要依据。     

血浆纤维蛋白原与动脉粥样硬化：值得关注的缺血性卒中治疗靶点

关于缺血性卒中急性期治疗,发病3h内重组组织型纤溶酶原激活剂（recombinant human tissue-type plasminogen activator,rtPA）溶栓、阿司匹林抗血小板聚集治疗均取得了较为安全有效的结果。动脉粥样硬化是缺血性卒中最重要的病理基础,大量研究已证实血浆纤维蛋白原及其降解产物在动脉粥样硬化进程中起了非常重要的作用,高纤维蛋白血症（hyperfibrinogenmia）是卒中的独立危险因素,其升高与缺血性卒中的不良预后关系密切。因此,血浆纤维蛋白原应该是一个值得关注的缺血性卒中治疗靶点。尽管目前关于缺血性卒中的降纤治疗还存在不少争议。     

基于卒中登记的缺血性卒中亚型分布及危险因素分析

目的 了解徐州地区缺血性卒中OCSP临床分型及M-TOAST病因分型及其相关危险因素,为该地区缺血性卒中的治疗及预防提供参考依据.方法 运用卒中注册软件,采用前瞻性单中心登记方法,登记566例缺血性卒中患者的临床资料,研究缺血性卒中的亚型分布,并以卒中登记中96例出血性卒中患者为对照,研究缺血性卒中的相关危险因素.结果 566例缺血性卒中患者中,脑梗死505例,TIA61例.部分前循环是最多见的缺血性卒中亚型,共243 例（48.12%）.脑梗死病因学分型M-TOAST分型中,动脉粥样硬化性血栓形成（AT）最多,共248例（49.11%）.高血压、吸烟、饮酒、高同型半胱氨酸是缺血性卒中最常见的危险因素.相对于出血性卒中,与缺血性卒中关系更为密切的是房颤、高同型半胱氨酸（OR=3.854,2.922）.结论 本研究中缺血性卒中OCSP分型中部分前循环梗死最多见,其病因学分型动脉粥样硬化性血栓形成 （AT）最多.相对出血性卒中,与缺血性卒中密切相关的是房颤、高同型半胱氨酸.     

颅内外动脉粥样硬化评价

缺血性卒中由于发病率、病残率、病死率和复发率高,给社会和家庭带来巨大负担。颅内和颈部动脉粥样硬化是导致缺血性卒中发生和复发的重要原因。因此,对颅内和颈部动脉粥样硬化进行全面评价,以预测脑卒中发生风险并指导临床决策,具有重要临床意义。本文就颅内和颈部动脉粥样硬化的主要评价指标和常用评价手段进行简要概述。     

Stroke and its modification in Parkinson's disease

Previous studies have not agreed on the incidence of ischemic stroke in persons with Parkinson's disease. There are epidemiologic and neurochemical facets of Parkinson's disease that might confer some benefit or protection against ischemic stroke. We used a case-control method to determine the lifetime history of ischemic stroke in 200 patients with Parkinson's disease and 200 controls of a similar age range. Analysis was also carried out for myocardial infarction as a marker of generalized atherosclerotic disease and for stroke risk factors. The cumulative incidence of ischemic stroke was significantly less in the patients with Parkinson's disease than in the controls, as was the cumulative incidence of myocardial infarction. Among risk factors, significantly fewer patients with Parkinson's disease used tobacco than controls. The decreased incidence of ischemic stroke in the patients with Parkinson's disease appears to be related to their less severe generalized atherosclerosis, possibly due to their lower incidence of tobacco use. In view of the known potential for dopamine to exacerbate experimental ischemic tissue damage, the possibility that the dopamine deficiency in the central nervous system of persons with Parkinson's disease confers an additional specific protective benefit against ischemic stroke cannot be excluded and requires further study.     

Targeting neutrophils in ischemic stroke: translational insights from experimental studies

Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood–brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis. Thrombosis is promoted through interactions with platelets, clotting factors, and release of prothrombotic molecules. In atherosclerosis, neutrophils promote plaque formation and rupture by generating oxidized-low density lipoprotein, enhancing monocyte infiltration, and degrading the fibrous cap. In experimental studies targeting neutrophils can improve stroke. However, early human studies have been met with challenges, and suggest that selective targeting of neutrophils may be required. Several properties of neutrophil are beneficial and thus may important to preserve in patients with stroke including antimicrobial, antiinflammatory, and neuroprotective functions.     

Increased leukocyte adhesiveness/ aggregation in patients with recurrent TIA

Objective - White blood cells might have a pathogenetic role in ischemic vascular conditions. Several studies have suggested that increased adhesiveness of these cells could contribute to such a damage. The present study was undertaken in order to examine the adhesive properties of leukocytes in the peripheral blood of patients with various degrees of ischemic neuro-vascular diseases. Methods - The percentage of aggregated white blood cells was determined by using a direct slide test. Results - The respective values of aggregated cells in 28 patients with major stroke, 11 with minor stroke, 17 with a single TIA, 11 with recurrent TIAs and 18 controls were 15.9±7.4%, 6.6±3.3%, 3.0±2.6%, 10.9±8.4% and 1.5±0.4%. The difference between patients with a single TIA and those with recurrent TIAs being significant at P <0.05. Conclusion - Being a sensitive marker of inflammation, our test might reveal the presence of an underlying smoldering inflammation in patients with recurrent TIA. These results are in agreement with modern studies that show that inflammation is an important feature of atherosclerosis.     

Genetic Variants on Chromosome 10q11.21 are Associated with Ischemic Stroke in the Northern Chinese Han Population

Genome-wide association studies have revealed two loci (rs1746048 and rs501120) on chromosome 10q11.21 associated with atherosclerosis. The genetic variants are related to chemokine (C-X-C motif) ligand 12, which has been shown to affect atherosclerosis. This study aims to explore the associations between these loci and risk of ischemic stroke in the northern Chinese Han population. A total of 368 patients with ischemic stroke and 381 healthy controls were included in the study. The single-nucleotide polymorphisms rs501120 and rs1746048 were analyzed by polymerase chain reaction–ligation detection reaction methods. Increased risk of ischemic stroke was associated with rs1746048 in a dominant mode. The CT + TT genotype of rs1746048 was represented at an increased frequency among patients with ischemic stroke. The genotype and allele frequencies of rs501120 were similar between patients with ischemic stroke and controls. However, the rs501120 CT + CC genotype and C allele were associated with an increased risk of ischemic stroke in the male subgroup. These correlations still remained after adjusting for confounding risk factors of stroke. Here, we present a study indicating that genetic variation on chromosome 10q11.21 might contribute to stroke susceptibility.     

Serial measurement of surface expressions of CD63, P-selectin and CD40 ligand on platelets in atherosclerotic ischemic stroke. A possible role of CD40 ligand on platelets in atherosclerotic ischemic stroke

BACKGROUND: Platelet activation is a key step in the progression of atherosclerosis. The CD40 ligand (CD40L) on platelets may be a critical factor to develop the acute vascular events from atheroma. METHODS: To determine the role of CD40L on platelets in atherosclerotic ischemic stroke, we serially measured the expressions of CD63, P-selectin and CD40L on platelets in patients with atherosclerotic ischemic stroke (n = 25) and compared them with those in patients with asymptomatic carotid stenosis (n = 20) and in normal subjects (n = 24). RESULTS: The expressions of CD63 and P-selectin on platelets were significantly higher in patients with atherosclerotic ischemic stroke (n = 25) than in normal subjects (n = 24). The extents of surface expressions of CD63 and P-selectin on platelets showed no significant differences between atherosclerotic ischemic stroke and asymptomatic carotid stenosis. However, the CD40L expression on platelets was significantly higher in atherosclerotic ischemic stroke when compared to that in asymptomatic carotid stenosis. CONCLUSIONS: In our data, among the population with large artery atherosclerosis, the patients with symptomatic ischemic events showed a significantly elevated expression of CD40L on platelets compared to those without ischemic events. Therefore, the upregulation of CD40L on platelets may be a specific marker of platelet activation to provoke ischemic stroke from large artery atherosclerosis.     

颈动脉粥样硬化与进展性缺血性脑卒中的关系

目的探讨颈动脉粥样硬化与进展性缺血性脑卒中的关系。方法采用彩色多普勒超声仪对564例缺血性脑卒中患者的颈动脉进行评估，比较进展性缺血性脑卒中和非进展性缺血性脑卒中患者的颈动脉粥样硬化特征和程度。结果564例缺血性脑卒中患者有135例为进展性缺血性脑卒中（23.8％）；在重度颈动脉粥样硬化110例中，有49例（44.5％）发展为进展性卒中；在重度颈动脉狭窄95例中，有48例（50．5％）发展为进展性卒中；在病理表现为溃疡斑86例中，有47例（54．7％）发展为进展性卒中：无颈动脉粥样硬化或伴轻度颈动脉粥样硬化的缺血性脑卒中患者，仅9％～10％发生进展性卒中。经Logistic回归分析发现，颈动脉粥样硬化程度、狭窄程度以及溃疡斑与进展性缺血性卒中的发生成正相关。结论颈动脉粥样硬化与进展性缺血性脑卒中的发生密切相关，颈动脉粥样硬化的严重程度可作为进展性缺血性脑卒中的预测指标。     

Albuminuria, but not metabolic syndrome, is a significant predictor of stroke recurrence in ischemic stroke

The aim of this study is to determine if there was an association of stroke recurrence with metabolic syndrome (MetS), defined by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-III) report or the International Diabetes Federation (IDF), as well as with other risk factors, including albuminuria. From February 1, 2004 to February 5, 2006, 523 patients were admitted to our Stroke Care Unit within 7 days of stroke onset. After excluding 22 patients who died in hospital and 27 patients who did not provide consent, 474 survivors (M/F=313/161, median age, 71 years) were enrolled. End-point events were fatal or nonfatal stroke. Diagnosis of MetS by NCEP-III criteria was made in 33% of patients, and by IDF criteria in 26%. During follow-up (505.4 person-years), 2 patients dropped out. Forty-nine patients among 370 with ischemic stroke and 5 patients among 102 patients with brain hemorrhage had stroke recurrence, being fatal in 3. A significant predictor of recurrence was albuminuria (HR: 1.835, 95% CI: 1.005-3.350) in ischemic stroke. There were no significant predictors of stroke recurrence in patients with brain hemorrhage. In conclusion, albuminuria, but not MetS, was a significant predictor of stroke recurrence in ischemic stroke.