急性脑梗死患者血浆生长分化因子15表达与预后的关系

目的探讨血浆生长分化因子15(GDF-15)与急性脑梗死患者临床预后的关系。方法选择102例入住我院神经内科的急性脑梗死患者,发病6h~7d内抽取血液标本,放免法测定GDF-15,分别在7d和90d采用改良的Rankin评分(mRS)对神经系统进行评估,将评估结果分为有利(mRS 0或1)或不利(mRS>1)两种。结果症状发作6h后GDF-15浓度明显升高,7d后开始降低。mRS>1的患者第7天和第90天GDF-15浓度明显高于mRS 0或1的患者。逻辑回归分析发现,发病后6h~7d,患者的GDF-15浓度与第7~90天的mRS评分有关。结论急性脑梗死患者血浆GDF-15浓度升高,可作为神经功能预后的生物标志物。     

Association of cerebral microbleeds in acute ischemic stroke with high serum levels of vascular endothelial growth factor

OBJECTIVE To determine whether vascular endothelial growth factor (VEGF) levels are associated with the presence of cerebral microbleeds (CMBs) in patients after acute ischemic stroke. DESIGN A cross-sectional study that used blood samples obtained within 24 hours of symptom onset from patients who experienced acute stroke to measure VEGF levels by enzyme immunoassay. A validated CMB rating scale was used to analyze acutely acquired magnetic resonance images, with the rater blind to clinical details and VEGF levels. SETTING Accident and Emergency Department at University College Hospital, London, England. PATIENTS Twenty patients who experienced acute ischemic stroke. MAIN OUTCOME MEASURES Presence of CMBs and serum level of VEGF. RESULTS Five of the 20 patients with acute ischemic stroke (25%) had CMBs. The median VEGF level in the CMB group was significantly higher than that in the group without CMBs (P?=?.003). CONCLUSION An increase in vascular permeability secondary to a raised VEGF level may have a role in the genesis of CMBs in patients with acute ischemic stroke.     

血清小而密低密度脂蛋白与急性缺血性脑卒中及预后的关系

目的探讨血清小而密低密度脂蛋白(sdLDL)与急性缺血性脑卒中(AIS)发生及预后的相关性。方法测定338例AIS患者(AIS组)和103例排除脑血管疾病患者(对照组)的血清sdLDL水平。AIS组患者根据临床常用的TOAST分型标准进行分型,并根据有无sdLDL异常进行分组,90 d后采用mRS评分评价患者的预后。结果与对照组相比,AIS组异常sdLDL发生率较对照明显增高,其中大动脉粥样硬化型卒中(LAA)亚组异常sdLDL所占比率较对照组明显升高,差异有统计学意义(均P<0.05)。在AIS组内,sdLDL异常亚组中男性、高血压和冠心病比率,总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、三酰甘油(TG)水平及90 d mRS评分、90 d NIHSS评分均显著高于sdLDL正常亚组(均P<0.05)。与预后良好组患者比较,预后不良组患者中男性、异常sdLDL所占比率明显偏高(均P<0.05),但高血压、高血脂、冠心病、心房纤颤及同型半胱氨酸血症所占的比率无明显统计学差异。行多因素Logistic回归分析显示,男性(OR=0.82,P<0.05)、冠心...     

急性缺血性卒中患者血清胱抑素C水平与脑白质疏松严重程度的相关性研究

目的探讨急性缺血性卒中患者血清胱抑素C水平与脑白质疏松严重程度的相关性。方法选择192例行头颅MRI检查的急性缺血性卒中患者,应用Fazekas评分量表将合并脑白质疏松的急性缺血性卒中患者分为轻度组27例,中度组96例,重度组69例。收集3组患者包括血清胱抑素C水平在内的各项临床资料。结果年龄、三酰甘油、肌酐等在3组间比较差异有统计学意义(均P<0.05),轻度组、中度组、重度组血清胱抑素C水平依次升高,差异均有统计学意义(均P<0.05)。有序多分类Logistic回归分析显示血清胱抑素C水平是脑白质疏松严重程度增加的独立危险因素(OR=4.669,P=0.042);Spearman相关分析显示,血清胱抑素C水平与脑白质疏松严重程度呈正相关(r=0.371,P=0.000)。结论血清胱抑素C水平升高与急性缺血性卒中患者脑白质疏松的严重程度独立相关。     

Retroviral lineage analysis of fibroblast growth factor receptor signaling in FGF2 inhibition of oligodendrocyte progenitor differentiation

Fibroblast growth factor 2 (FGF2) inhibits oligodendrocyte progenitor cell (OPC) differentiation during development and limits remyelination following chronic demyelination. The current study examines the mechanism underlying this effect of FGF2 expression on OPC differentiation. Retroviral lineage tracing demonstrates a direct in vivo effect of FGF receptor (FGFR) signaling on OPC differentiation. Retrovirus expressing a dominant negative FGFR construct (FGFRdn) and green fluorescent protein (GFP) was injected into the dorsal columns of postnatal day 7 (P7) mice followed by perfusion at P28. Among the GFP-labeled cells, FGFRdn retrovirus generated a higher proportion of oligodendrocytes than did control infections. This result from FGFRdn expression in OPCs was similar to the result obtained in our previous study using control retrovirus in FGF2 null mice. Further, in vitro retroviral siRNA expression distinguishes the function of specific FGFR isoforms in OPC responses to FGF2. FGF2 inhibition of OPC differentiation was effectively blocked by siRNA targeted to FGFR1, but not FGFR2 or FGFR3. We propose a model of direct FGF2 activation of FGFR1 leading to inhibition of OPC differentiation. This signaling pathway may be an important regulator of oligodendrocyte generation during myelination in development and may perturb OPC generation of remyelinating oligodendrocytes in demyelinating disease.     

奥拉西坦联合鼠神经生长因子治疗脑卒中的疗效观察

目的探讨奥拉西坦联合鼠神经生长因子对脑卒中患者的临床疗效及预后的影响。方法选取242例脑卒中患者为研究对象,根据其治疗顺序分成A、B 2组,各121例。B组予以奥拉西坦静滴,A组予以奥拉西坦与鼠神经生长因子联合用药。对比2组治疗前后神经功能改善情况,行18~24个月随访,观察生活自理能力及运动功能改善情况。结果治疗后,2组NFDS、NIHSS等神经功能评分均较治疗前显著降低,且Fugl-Meyer评分较治疗前明显提高(P0.05);其中A组各指标改变幅度大于B组(P0.05);18~24个月的随访中,A组ADL优良率82.6%,显著高于B组的49.6%(P0.05)。结论对脑卒中患者予以奥拉西坦联合鼠神经生长因子静滴疗效确切,可有效改善生活质量,值得临床推广。     

Cryptogenic cerebral infarction in a young patient with very high lipoprotein(a) serum level as the only risk factor

Abstract Lipoprotein(a) [Lp(a)] is a plasma lipoprotein that consists of a low-density lipoprotein (LDL)-like particle containing APO B-100 and apolipoprotein(a), linked by a disulphide bridge. There is evidence that higher serum level of Lp(a) is a predictor of various vascular diseases, such as myocardial infarction, coronary stenosis, re-occlusion of aortocoronary bypass vein grafts, peripheral atherosclerosis and cerebral infarction [1–4]. We describe a young man with a cryptogenic stroke with very high serum level of Lp(a) as the only vascular risk factor.     

Effects of neuroserpin on clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke

Objective: Neuroserpin (NSP) is known for its neuroprotective effects. The aim of this study was to investigate the relationship between NSP level and clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke.

Methods: A total of 133 patients with acute cerebral infarction (ischemia group) and 44 controls were recruited. The modified Rankin Scale (mRS) was used to determine the functional outcome three months after onset. We investigated the relationship between serum NSP levels [on admission and a decrease in NSP levels (10 days after admission versus on admission)] and serum levels of several inflammatory markers.

Results: We confirmed that NSP levels on admission in the ischemia group were significantly higher than those in the control group. NSP levels in patients with good outcomes were significantly higher than those in patients with poor outcomes. NSP levels on admission were associated with having a good outcome in these patients. We found that a larger decrease in NSP levels (on admission vs. 10 days after admission) was correlated with lower serum levels of IL-6, IL-1β, and ICAM-1 10 days after admission.

Conclusions: A larger decrease in NSP levels related to lower levels of inflammatory marker, while higher NSP levels were associated with lower inflammatory markers and better functional outcomes. Decreasing the infarct size may play a role in this process. These results provide more evidence of the neuroprotective effect of NSP in cerebral ischemic patients. Decrease in the Serum NSP level and NSP level at admission may be considered as potential predictive factors for outcome of acute ischemic stroke.     

Insulin-like growth factor-1 receptor polymorphism and ischemic stroke: a case-control study in Chinese population

Objectives – Low levels of insulin‐like growth factor 1 (IGF‐1) are associated with atherosclerosis, and insulin‐like growth factor‐1 receptor (IGF‐1R) polymorphisms can change plasma levels of IGF‐1 and may alter the function of the receptor. Whether there is any association of genetic variation in IGF‐1R gene with ischemic stroke (IS) is presently unknown. Materials and methods– A 1:1 case–control study was conducted. The G → A polymorphism of IGF‐1R gene (rs2229765) were analyzed by TaqMan SNP genotyping technique in Chinese patients with IS (n = 309) and old subjects without IS (n = 309). Results– The frequency of A allele in the patients and controls was 45.79% and 39.64%, respectively. The AA genotype distribution of IGF‐1R gene was significantly higher in the patients (27.51%) than controls (18.23%; P = 0.022). Conditional logistic regression revealed that the AA genotype of IGF‐1R was associated with IS (OR = 1.641, P = 0.022). After adjustment for smoking, alcohol drinking, history of hypertension, and body mass index, IGF‐1R AA genotype was still significantly associated with an increased risk of IS (OR = 1.787, P = 0.029), compared with IGF‐1R GG. Conclusions– The G → A polymorphism in IGF‐1R gene may affect the susceptibility to IS in Chinese population.     

急性脑梗死患者血清血管内皮生长因子的测定

目的　探讨急性脑梗死与血管内皮生长因子 (VEGF)的关系。方法　对 3 0例急性脑梗死患者和 40例健康人血清血管内皮生长因子含量进行测定。患者采血时间为病后第 2天或第 3、4天 ,取均数与对照组比较。结果　 3 0例急性脑梗死患者血清 VEGF含量为 (2 95 .0 4± 3 5 .73 ) pg/ ml,对照组为 (13 7.71± 11.5 3 ) pg/ m l,两组比较差异显著。结论　急性脑梗死患者血清 VEGF升高 ,提示 VEGF是脑梗死急性期的自我保护机制之一。     

血浆胰岛素样生长因子-1水平变化对急性缺血性脑卒中患者预后的影响

目的探讨血浆胰岛素样生长因子-1与急性缺血性脑卒中之间的关系。方法74例急性缺血性脑卒中患者,分别于发病48h内(第1次)、7d～8d(第2次)和12d～14d(第3次)采集血液标本,采用固相酶联化学荧光免疫分析方法检测血浆胰岛素样生长因子-1水平,并与对照组进行比较。脑卒中患者于发病后48h内(急诊首诊时)及发病后12d～14d进行两次神经功能缺损程度评分(CSS1和CSS2),通过两次评分的差值(CSS1-CSS2)判断预后。结果74例急性缺血性脑卒中患者第1、2次血浆胰岛素样生长因子-1检测水平明显低于正常对照组(t=3.713,2.032;P<0.05或P<0.01)。比较不同梗死面积组之间血浆胰岛素样生长因子-1水平的变化显示,大面积梗死组患者血浆胰岛素样生长因子-1水平最低,与中、小梗死面积组相应时限比较差异有统计学意义(P<0.05或P<0.01)。不同预后组之间,以病情加重组患者第1次血浆胰岛素样生长因子-1检测水平最低,与其他各组(明显改善、改善、无变化及对照组)相同时限测值相比差异有统计学意义(均P<0.01)。相关性分析显示,两次神经功能缺损程度评分差值与3次不同时限血浆胰岛素样生长因子-1水平均存在明显相关性(P<0.05或P<0.01)。结论(1)胰岛素样生长因子-1可能参与急性缺血性脑卒中的病理生理学机制,对缺血性脑卒中患者有神经保护作用,可能成为急性缺血性脑卒中的一种治疗方法。(2)血浆胰岛素样生长因子-1对判断急性缺血性脑卒中患者的临床预后有一定价值,特别是根据发病48h内其水平变化的情况能够及早判断患者预后。     

亚甲基四氢叶酸还原酶基因多态与河南汉族人群缺血性脑血管病的相关性

目的 研究亚甲基四氢叶酸还原酶(MTHFR)2个常见位点的突变与缺血性脑血管病发病的相关性.方法 选取病例组470例,对照组495名,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术和TaqMan-MGB探针分型方法进行基因分型.结果 病例组C677T突变的T等位基因突变频率为61.9%,对照组为45.1%,两组相比较差异有统计学意义(X~2=55.089,P＜0.01,OR=1.983,95%CI 1.653～2.378);病例组与对照组C677T多态基因型频率CC、CT、TT型分别为16.6%、43.0%、40.4%及36.6%、36.8%、26.7%,两组间比较CT型(X~2=3.882,P＜0.05,OR=1.296,95% CI 1.001～1.678),TT型(X~2=20.527,P＜0.01,OR=1.866,95%CI 1.423～2.448)分布差异均有统计学意义.病例组与对照组A1298C突变的C等位基因突变频率分别为13.1%和11.2%,基因型频率AA、AC、CC型分别为75.3%、23.2%、1.5%及78.2%、21.2%、0.6%,两组相比A1298C多态的等位基因频率和基因分型的差异均无统计学意义.结论 C677T突变与缺血性脑血管病的发生显著相关,可能是预测河南汉族人群缺血性脑血管病的风险因子,A1298C突变与河南汉族人群缺血性脑血管病无关.     

Association between pneumonia in acute stroke stage and 3-year mortality in patients with acute first-ever ischemic stroke

The influence of pneumonia in acute stroke stage on the clinical presentation and long-term outcomes of patients with acute ischemic stroke is still controversial. We investigate the influence of pneumonia in acute stroke stage on the 3-year outcomes of patients with acute first-ever ischemic stroke. Nine-hundred and thirty-four patients with acute first-ever ischemic stroke were enrolled and had been followed for 3 years. Patients were divided into two groups according to whether pneumonia occurred during acute stroke stage or not. Clinical presentations, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. The result showed that a total of 100 patients (10.7%) had pneumonia in acute stroke stage. The prevalence of older age, atrial fibrillation was significantly higher in patients with pneumonia in acute stroke stage. Total anterior circulation syndrome and posterior circulation syndrome occurred more frequently among patients with pneumonia in acute stroke stage (P < 0.001 and P = 0.009, respectively). Multivariate Cox regression revealed that pneumonia in acute stroke stage is a significant predictor of 3-year mortality (hazard ratio = 6.39, 95% confidence interval = 4.03–10.11, P < 0.001). In conclusion, pneumonia during the acute stroke stage is associated with increased risk of 3-year mortality. Interventions to prevent pneumonia in acute stroke stage might improve ischemic stroke outcome.     

急性缺血性卒中NEW-TOAST分型各亚型与血糖的关系

目的 研究急性缺血性卒中NEW-TOAST分型各亚型与血糖的关系。方法 回顾性分析624例住院急性缺血性卒中患者的病史及相关检查结果,按NEW-TOAST分型标准对所有患者进行分型,并对各亚型的血糖水平分布资料进行多分类资料的关联分析,比较各亚型糖代谢异常及糖化血红蛋白异常的频率,然后计算血糖、血压和血脂的优势比（OR）及95％的置信区间(CI)。结果 (1) 624例患者NEW-TOAST分型中,以动脉粥样硬化血栓形成型(AT)为主,小动脉闭塞型(SAO)次之;其中原有糖尿病病史119例(19.1％),新发现糖尿病40例(7.5％),糖调节受损71例(11.4％);(2)AT、SAO患者糖代谢异常及糖化血红蛋白的比例均较高,分别为40.4％、39.7％及48.6％、48.1％;各亚型与高血糖的关联分析,x2=14.83,P=0.020,r=0.152。SAO患者高血糖的OR为1.925,95％ CI 1.392 ～2.664,AT患者与高血糖无明显相关;AT患者高血压的OR为2.874,95％ CI1.957 ～4.222,SAO患者高血压的OR为1.609,95％ CI 1.100 ～1.235;各亚型与高低密度脂蛋白胆固醇(LDL-C)的关联分析,SAO患者高LDL-C的OR为1.419,95％CI1.026 ～ 1.962,AT与高LDL-C无明显相关;(3)各亚型糖代谢异常频率差异的比较：x2=17.79,P=0.000,AT及SAO分别与其他3型相比,均P＜0.05;而各亚型糖化血红蛋白异常频率差异的比较：x2=35.57,P=0.000,两两比较发现,AT与SAO,x2=0.014,P=0.906;AT及SAO分别与其他3型相比,均P＜0.05。结论 急性缺血性卒中NEW-TOAST分型中以AT、SAO所占比例更高;各亚型与血糖水平有关联性,且SAO与血糖关联最为密切;高血压对大小血管均有损伤作用,高LDL-C可能对小血管的损伤较明显。     

Association of E-selectin gene polymorphisms with ischemic stroke in a Chinese Han population

The E-selectin gene, a member of the selectin superfamily of adhesion molecules, plays an important role in the pathogenesis of thrombovascular diseases. The present study was designed to investigate the potential relationship between E-selectin gene polymorphisms and ischemic stroke in a Chinese Han population. Three hundred fourteen ischemic stroke patients and 389 unrelated healthy controls were recruited for the study. Three single-nucleotide polymorphisms (SNPs)-rs1805193(G98T), rs5361(A561C), and rs5355(C1839T)-in the exon region of the E-selectin gene, were genotyped using a Multiplex SNaPshot sequencing assay. The data showed that the genotype and allele frequencies of G98T and C1839T SNP were similar in both ischemic stroke patients and the controls. In contrast, the frequency of both the AC genotype and the C allele of A561C was significantly higher in ischemic stroke patients than in healthy controls (P = 0.001, P < 0.001, respectively). After adjusting for other risk factors (such as hypertension, diabetes, tobacco smoking, and alcohol consumption), the E-selectin gene AC genotype and C allele of A561C were still associated with a risk of ischemic stroke (odds ratio [OR] = 2.73, 95% confidence interval (CI): 1.29-5.76, P = 0.008; OR = 2.80, 95% CI: 1.58-4.94, P < 0.001, respectively). Our current study demonstrates that the E-selectin SNP A561C is associated with increased risk for the development of ischemic stroke in this subset of the Han Chinese population.     

Increased levels of serum basic fibroblast growth factor in schizophrenia

Basic fibroblast growth factor (bFGF) is a multifunctional growth factor that has been implicated in a variety of neurodevelopmental processes. The aim of the present study was to examine whether bFGF contributes to the pathophysiology of schizophrenia. Serum bFGF levels in 40 patients with schizophrenia (15 drug-naive and 25 medicated patients) and in 40 age- and sex-matched healthy normal controls were measured. Serum bFGF levels were significantly higher in the medicated patients than in the normal controls. Analysis of partial correlation coefficients showed that the increased bFGF levels might not be attributable to antipsychotic medication. Although there was no significant overall difference in bFGF levels between drug-naive patients and normal controls, the bFGF levels in these patients significantly correlated with the severity of negative symptoms. Furthermore, we found a significant negative correlation between serum bFGF levels and the age of onset in the entire patient group. Our finding of elevated bFGF levels in the serum of patients with schizophrenia, especially in earlier age-of-onset cases considered to have more neurodevelopmental insults, suggests that bFGF abnormalities may be involved in the pathophysiology of schizophrenia.     

Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients

The presence of an inflammatory response in the pathophysiology of acute brain ischemia is relatively well established, but less is known about the anti-inflammatory mechanisms. The aim of the present study was to evaluate part of the immune response in acute stroke patients and to analyze a possible correlation with other hematological parameters, clinical outcome, size of infarct and subtypes of strokes. We prospectively studied 42 stroke patients, without signs of infections or inflammatory diseases, at days 0, 1, 3, 7 and 14, and 39 healthy control subjects. We measured serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine interleukin-6 (IL-6) by ELISA method. We observed a highly inverse correlation between these two molecules in control subjects (r=−0.78, p=0.0000001), and this correlation was lost in stroke patients. Patients had significantly lowered IL-10 serum levels soon after the acute event (p=0.00005), with a slight increase at the seventh day. On the other hand, patients had increased IL-6 serum levels compared with controls after day one until day 14 (p<0.04), with a maximum increase at day 3. Interleukin-6 correlated with clinical outcome whereas interleukin-10 did not. Low levels of interleukin-10 indicate that the anti-inflammatory response is down-regulated in acute stroke patients. The pro-inflammatory response begins 24 hours after the onset of acute cerebral ischemia, as indicated by the increased serum levels of interleukin-6. The physiological balance between these two molecules is altered in acute stroke patients. Received: 9 March 2001 / Accepted in revised form: 25 October 2001     

Association of interleukin-1 gene cluster polymorphisms with ischemic stroke in a Chinese population

BACKGROUND AND AIMS: Chronic inflammatory process plays an important role in atherothrombosis. Interleukin-1 (IL-1) is one of the key modulators of the inflammatory response and its activity is critically regulated by its receptor antagonist (IL-1Ra). A variable number tandem repeat polymorphism in intron 2 of IL-1Ra gene and a C to T single base polymorphism in the promoter of IL-1beta gene (C(-511)-->T) have been reported to affect the levels of IL-1 as well as its antagonist, IL-1Ra. It is also reported in several studies that these polymorphisms are associated with the susceptibility to cardio-cerebral vascular disease. However, data are limited in China. In this article, we studied the relationships between these polymorphisms and the risk of ischemic stroke in China. MATERIALS AND METHODS: One hundred and twelve patients committed ischemic stroke were compared with 95 demographically matched healthy volunteers. RESULTS: The frequencies of the IL-1Ra 1/1 genotype and IL-1Ra allele 1 (Ra*1 allele) in stroke patients were significantly higher than those in healthy volunteers [93.7% vs. 82.1%, P =0.014; 0.964 vs. 0.905, P =0.007]. No significant differences were found in the IL-1beta -511 genotype and the allele distribution between the two groups. CONCLUSIONS: Our results implicated that IL-1 gene polymorphism might be associated with the susceptibility to ischemic stroke.     

The 15-LO-1/15-HETE system promotes angiogenesis by upregulating VEGF in ischemic brains

Objectives: Angiogenesis promotes neurobehavioral recovery after cerebral ischemic stroke. 15(S)-hydroxyeicosatetraenoic acid (15-HETE) is one of the major metabolites of arachidonic acid by 15-lipoxygenase (15-LO) and stimulates the production of vascular endothelial growth factor (VEGF), thus, inducing autocrine-mediated angiogenesis. The present study aimed to investigate the role of 15-LO/15-HETE system on VEGF expression and angiogenesis in brain ischemia.

Methods: Rat cerebral arterial vascular endothelial cells were used to set up a cell injury model of oxygen-glucose deprivation and reoxygenation (OGD/R), mimicking a condition of brain ischemia. A mouse model of middle cerebral artery occlusion (MCAO) was established.

Results: Oxygen-glucose deprivation increased cellular expression of 15-LO-1 and VEGF. Transfection of 15-LO-1 siRNA depleted cells of 15-LO-1, and sequentially induced downregulation of VEGF expression; while, incubation of 15-HETE increased the expression of VEGF. Incubation of 15-HETE attenuated the reduction in cell viability induced by oxygen-glucose deprivation, and promoted cell migration, while transfection of 15-LO-1 siRNA showed an opposite effect. In animal experiments, the density of microvessels in hypoxic regions of brains was significantly increased after MCAO, while intracerebroventricular delivery of 15-LO-1 siRNA significantly reduced the density of microvessels, and downregulates VEGF expression.

Discussion: The results indicate that the 15-LO-1/15-HETE system promotes angiogenesis in ischemic brains by upregulation of VEGF, representing a potential target for improving neurobehavioral recovery after cerebral ischemic stroke.