VEGF overexpression enhances striatal neurogenesis in brain of adult rat after a transient middle cerebral artery occlusion

To elucidate whether vascular endothelial growth factor (VEGF) improves stroke-induced striatal neurogenesis, we intraventricularly injected human VEGF(165)-expressive plasmid (phVEGF) mixed with liposome into adult rats after a transient middle cerebral artery occlusion (MCAO). The results showed that EGFP, a reporter protein, positive cells appeared at 2 hr, further enhanced at 4 hr, reached the maximum at 3 days and still remained at 14 days after a single injection. Treatment with phVEGF increased angiogenesis, as indicated by double staining of vWF, a marker of endothelial cells, and 5'-bromodeoxyuridine (BrdU), a marker of cell proliferation. The phVEGF treatment dose-dependently reduced infarct volume of brain at 2 weeks after MCAO. The neuroprotection by VEGF could be obtained when the plasmid was injected within 2 hr after stroke. Moreover, VEGF overexpression significantly increased cell proliferation in the ipsilateral SVZ and the numbers of BrdU(+)-CRMP-4(+) and BrdU(+)-Tuj1(+), two markers of immature newborn neurons, and BrdU(+)-MAP-2(+), a marker of mature newborn neurons, cells in the ipsilateral striatum to MCAO. Present results show that VEGF plasmid treatment after stroke can significantly reduce infarct volume and enhance striatal neurogenesis in adult rat brain. This suggests that VEGF overexpression acquires significant functions of neuronal protection and repair in the injured brain, which provides a possibility to develop a novel therapeutic strategy for the patients with stroke.     

Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic–ischemic model at 24 h post-injury

PURPOSE: In a neonatal rat model of hypoxic-ischemic (HI) brain injury, using T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), we aim to determine the best MRI method of lesion quantification that reflects infarct size. MATERIALS AND METHODS: Twenty 7-day-old rats underwent MRI 24h after HI brain injury was induced. Lesion size relative to whole brain was measured using T2WI and apparent diffusion coefficient (ADC) maps, applying thresholds of 60%, 70% and 80% contralateral control hemisphere mean ADC, and at day 10 post-HI on pathology with TTC staining. Multiple linear regression analysis was used to study the relationships between lesion size at MRI and pathology. RESULTS: Lesion size measurement using all MRI methods significantly correlated with infarct size at pathology; using T2WI, r=0.808 (p<0.001), using 80% ADC, 70% ADC and 60% ADC thresholds, r=0.888 (p<0.001), 0.761, (p<0.001) and 0.569 (p=0.014), respectively. Eighty percent ADC threshold was found to be the only significant independent predictor of final infarct volume (adjusted R(2)=0.775). CONCLUSION: At 24h post-HI, lesion size on DWI, using 80% ADC threshold is the best predictor of final infarct volume. Although T2WI performed less well, it has the advantage of superior spatial resolution and is technically less demanding. These are important considerations for experiments which utilize MRI as a surrogate method for lesion quantification in the neonatal rat HI model.     

前循环动脉粥样硬化性短暂性脑缺血 发作的血管病变及预后影响因素

目的 探讨首发前循环动脉粥样硬化性短暂性脑缺血发作(TIA)的血管病变及预后影响因素。方法 收集121例首发前循环动脉粥样硬化性TIA患者,发病48 h内入院,应用CT血管造影和颈动脉超声评估血管病变,采用ABCD评分,观察1年内脑血管病的发生率,比较血管病变及ABCD评分对预后的影响。结果(1)121例患者中106例共258支血管狭窄; 71例(58.68%)存在同侧颈部及颅内动脉狭窄≥50%,66例(54.55%)存在多支血管狭窄,33例(27.27%)有Willis 环变异; 66例(54.55%)检出不稳定斑块;(2)随访1年脑血管病发生率18.18%; 多元Logistic回归分析显示除了高血压病、高脂血症、发作时间≥10 min外,同侧颈部及颅内动脉≥50%狭窄(OR=2.65,95% CI:1.30～5.38,P=0.007)是影响预后的独立危险因素; 同侧颈部及颅内动脉狭窄分层后发现,同侧颈部及颅内动脉中度狭窄患者发生脑血管病的比例是正常或轻度狭窄5.92倍(95%CI:1.20～29.27,P=0.029),而重度狭窄或闭塞发生比例是正常或轻度狭窄7.92倍(95%CI:1.75～35.83,P=0.007);(3)与未发生脑血管病组比较,发生脑血管病组的ABCD2、ABCD3和ABCD3-V评分的得分均显著升高(P≤0.01); 3种评分法预测1年内发生脑血管病风险的ROC曲线下面积分别为0.68、0.73和0.80,ABCD3-V评分预测预后准确度最高(P<0.05),最佳界值为7.5分。结论 首发前循环动脉粥样硬化性TIA的血管病变广泛并严重,1年内脑血管病发生率高,同侧颈部及颅内动脉狭窄严重程度及ABCD3-V评分能更准确预测患者的预后。     

SP600125对大鼠肝缺血再灌注损伤的保护作用

背景：SP600125作为JNK激酶抑制剂,可特异性阻断JNK细胞转导通路,对肝脏缺血再灌注又起到怎样的作用,目前尚无相关研究。 目的：应用SP600125对肝脏缺血再灌注进行干预,分析JNK信号转导通路在该病理生理过程中的作用。 方法：将30只雄性SD大鼠按随机数字表法分为3组,假手术组、缺血再灌注组及SP600125组各10只。假手术组仅行进腹手术;缺血再灌注组行进腹手术,阻断肝左中叶的血供;SP600125组于术前半小时腹腔注射SP600125 15 mg/kg,其他操作同缺血再灌注组。于复灌后2 h取材,分别测定各组血清肝功能酶活性,通过苏木精-伊红切片染色观察肝组织结构的病理变化,运用免疫组织化学法检测肝组织中p-JNK表达并进行半定量分析,以比色法检测肝脏丙二醛含量及髓过氧化物酶活性。 结果与结论：相对于缺血再灌注组,SP600125组血清肝功能酶活性明显下降,肝脏p-JNK表达较低,肝脏髓过氧化物酶活性以及丙二醛含量下降,病理损伤有所缓解。提示JNK细胞信号转导通路在肝缺血再灌注损伤过程中被广泛激活,应用JNK抑制剂SP600125对缺血再灌注损伤有保护作用。     

环磷腺苷葡胺联合奥扎格雷钠针治疗前循环脑梗死临床和实验室观察

目的探讨环磷腺苷葡胺联合奥扎格雷钠针治疗前循环脑梗死临床疗效和对凝血系统的影响。方法将80例前循环脑梗死患者进行随机分组,治疗组在对照组治疗的基础上,加用磷腺苷葡胺和奥扎格雷钠针,在治疗前、治疗14d,行神经功能缺损评分,在治疗前、治疗第7天,治疗14d,采血行APTT、PT检查,以判断疗效和对凝血系统的影响。结果治疗14d后治疗组NIHSS评分明显降低,与对照组比较差异有统计学意义（P〈0．01）,治疗前、治疗7d、治疗14d2组PT、APTT比较,差异无统计学意义（P〉0．05）。结论环磷腺苷葡胺联合奥扎格雷钠针治疗急性脑梗死患者临床效果明显,且对凝血系统没有影响。     

糖尿病患者下肢神经传导功能异常的特征分析

目的探讨糖尿病患者下肢神经传导功能异常的特征。方法搜集223例T2DM患者下肢神经传导检测资料,分析腓深、腓肠、胫神经传导功能。结果(1)158例神经传导异常,异常率70.85%,糖尿病病史1年内、1~4年、5~9年、10~30年异常率分别为61.54%、67.5%、71.19%、79.41%。(2)上述三神经传导速度(NCV)异常率分别为20.67%、16.86%、16.28%;腓深、胫神经波幅异常率为19.94%、11.73%,其末梢潜伏时(DL)异常率为8.94%、5.57%。(3)NCV减慢伴波幅降低和(或)DL延长占47.47%,单纯运动神经(MN)波幅降低占29.75%,单纯NCV减慢占16.46%,DL延长和(或)波幅降低占6.35%。结论(1)T2DM患者随病史延长,糖尿病周围神经病(DPN)发病率升高。(2)T2DM患者下肢神经中,腓深神经较易受累,腓肠神经次之,胫神经受累率低于前两者;在判断MN传导功能指标中,敏感性由高至低依次为NCV、波幅、DL。(3)DPN中,NCV减慢伴随波幅降低和(或)DL延长发生率高于单纯NCV减慢。     

不同条件髋部骨骼的短期精密度差异：双能X射线骨密度仪测量

背景：对骨密度测量的方法有多种多样,但对髋部不同程度骨质疏松测定方面的质量控制国内目前尚未见报道。 目的：比较应用DPX-MD双能X射线骨密度仪测量髋部不同程度骨质疏松骨的短期精密度差异。 方法：根据骨质疏松程度分类标准,将20例受试者分为骨量正常组、骨量减少组、骨质疏松组、严重骨质疏松组。1个附带软组织的死体髋部由川北医学院人体解剖实验室提供。采用DPX-MD双能X射线骨密度仪测量每例受试者髋部骨骼的骨密度,1次/d,连续测定5 d。各部位的骨密度值以均值±标准差表示,由不同骨密度的均值除标准差得到变异系数,即短期精密度。 结果与结论：髋部的股骨颈、Ward三角区、大转子、大转子内区、髋部总体这5个区域比较,各组每例受试者均为髋部总体骨密度的变异系数最小,说明髋部总体区的短期精密度最好,股骨颈次之,Ward三角区骨密度的变异系数最大,这可能与其难准确定位有关。骨量正常组骨密度变异系数小于骨量减少组、骨质疏松组、严重骨质疏松组,其短期精密度最好,死体各区域骨密度的变异系数值均大于上述4组,说明其短期精密度最差。结果提示不同条件髋部骨骼的短期精密度存在差异,在临床药物疗效观察过程中进行骨密度检测时,可选择影响最小的髋部总体区域,其次为股骨颈部位。     

脑血管支架种类及材料学特点与支架置入后的补体反应

目的：探讨脑血管支架材料学特点及补体反应与支架置入后并发症的关系。方法：以“脑血管支架,生物材料,生物相容性,再狭窄,补体反应”为中文检索词;以“rebrovascular disease,stent,therapy,complement”为英文检索词,采用计算机检索Pubmed数据库(http://www.ncbi.nlm.nih.gov/PubMed)及维普数据库(http://www.cqvip.com/)2000-01/2008-12有关脑血管支架材料学特点与支架置入后补体反应的文章;排除重复研究及Meta分析类文章。以24篇文献为主重点探讨了脑血管支架材料学特点及补体反应与支架置入后并发症的关系。结果：金属支架的生物相容性较差,聚合物支架、涂层支架和药物支架的生物相容性较好。脑血管支架作为治疗颅内外血管性疾病的一个重要手段,可降低颅内外动脉狭窄患者缺血性脑卒中的风险,但支架置入后的并发症如再狭窄等问题严重阻碍着该技术的进一步发展,免疫炎症反应在缺血性脑损伤机制中起着重要作用,生物材料对补体系统也有明显的影响。结论：选用合适的生物医用材料,脑血管支架置入治疗可明显降低脑血管病的死亡率。但要注意脑血管支架置入过程中以及置入后可能发生的并发症,给予积极的防治是非常重要的。研制新的生物医用材料,同时检测补体系统相关指标,将会提高脑血管支架置入治疗的成功率。关键词：脑血管支架;生物材料;生物相容性;再狭窄;补体反应doi:10.3969/j.issn.1673-8225.2010.29.031     

Presence of CSF oligoclonal bands (OCB) is associated with the HLA-DRB1 genotype in a West Australian multiple sclerosis cohort

High-resolution HLA-DRB1 genotyping was performed in 97 OCB-positive and 68 OCB-negative cases with demyelinating disease to determine the influence of HLA-DRB1 alleles on the presence of OCB in a West Australian multiple sclerosis (MS) cohort. Carriage of the HLA-DRB1*1501 allele was associated with both OCB-positive and OCB-negative MS compared with controls, but more strongly with the OCB-positive group, and increased the likelihood of having OCB 2.1-fold with evidence of a dominant dose–effect. The HLA-DRB1*0301 allele was negatively correlated with OCB, with all homozygotes OCB-negative, suggesting a possible recessive protective effect of HLA-DRB1*0301. There was no significant correlation between OCB and the DRB1*04 alleles which have been associated with OCB-negative MS in previous Swedish and Japanese studies. Evidence of allelic interactions was found with HLA-DRB1*1501/*1301 heterozygotes having a reduced frequency of OCB and HLA-DRB1*0301/*0401 heterozygotes all being OCB-negative. These findings confirm the strong association between HLA-DRB1*1501 and OCB which has been found in other populations but indicate that the influence of other HLA-DRB1 alleles varies in different populations. Our study is the first to show that HLA-DRB1 allele interactions and dose–effects influence the frequency of OCB.     

Stage-specific regulation of oligodendrocyte development by Hedgehog signaling in the spinal cord

Elucidation of signaling pathways that control oligodendrocyte (OL) development is a prerequisite for developing novel strategies for myelin repair in neurological diseases. Despite the extensive work outlining the importance of Hedgehog (Hh) signaling in the commitment and generation of OL progenitor cells (OPCs), there are conflicting reports on the role of Hh signaling in regulating OL differentiation and maturation. In the present study, we systematically investigated OPC specification and differentiation in genetically modified mouse models of Smoothened (Smo), an essential component of the Hh signaling pathway in vertebrates. Through conditional gain-of-function strategy, we demonstrated that hyperactivation of Smo in neural progenitors induced transient ectopic OPC generation and precocious OL differentiation accompanied by the co-induction of Olig2 and Nkx2.2. After the commitment of OL lineage, Smo activity is not required for OL differentiation, and sustained expression of Smo in OPCs stimulated cell proliferation but inhibited terminal differentiation. These findings have uncovered the stage-specific regulation of OL development by Smo-mediated Hh signaling, providing novel insights into the molecular regulation of OL differentiation and myelin repair.