脑源性神经营养因子基因重组慢病毒转染骨髓间质干细胞移植治疗大鼠脑出血的实验研究

目的 观察脑源性神经营养因子(BDNF)基因重组慢病毒转染骨髓间质干细胞(MSCs)移植治疗大鼠脑出血的疗效.方法 分离培养大鼠MSCs;将带有BDNF的慢病毒载体转染MSCs;RT-PCR、蛋白质印迹检测转基因MSCs BDNF基因及蛋白水平表达.制备大鼠脑出血模型,采用抽签法随机分为磷酸盐缓冲液(PBS)组、MSCs组、空病毒转染骨髓问质干细胞(MSCs-EGFP)组、脑源性神经营养因子基因重组慢病毒转染骨髓间质干细胞(MSCs-EGFP-BDNF)组,每组15只.72 h后细胞移植,记录各组细胞移植后7、14、21 d神经功能缺损改善程度;免疫荧光双标检测MSCs脑内迁移和分化情况.结果 MSCs-EGFP-BDNF组BDNF基因及蛋白水平表达明显高于MSCs组及MSCs-EGFP组;与PBS组(7 d:2.0±0.4,14 d:1.7 ±0.2,21 d:1.3±0.2)相比,MSCs组(7 d:1.6±0.2,14 d:1.2 ±0.3,21 d:0.8±0.2)、MSCs-EGFP组(7 d:1.6±0.3,14 d:1.1 ±0.2,21 d:0.8 ±0.3)及MSCs-EGFP-BDNF组(7 d:1.2±0.3,14 d:0.6±0.1,21 d:0.2 ±0.2)大鼠神经功能评分均有不同程度改善(F=6.667、18.417、20.882,均P＜0.05),其中MSCs-EGFP-BDNF组改善最为显著;免疫荧光双标显示MSCs-EGFP-BDNF组胶原纤维酸性蛋白、神经元特异性核蛋白、环核苷酸磷酸二酯酶阳性率明显高于MSCs组及MSCs-EGFP组,而MSCs组与MSCs-EGFP组比较差异无统计学意义.结论 BDNF基因重组慢病毒修饰的MSCs基因及蛋白水平表达均增高;修饰的MSCs移植后可迁移至脑出血灶周围存活并分化表达神经细胞标志物,促进脑出血后神经功能修复.     

骨髓间充质干细胞对实验性自身免疫性重症肌无力大鼠的治疗作用

目的探讨骨髓间充质干细胞对实验性自身免疫性重症肌无力大鼠模型的治疗作用及其可能机制。方法全骨髓贴壁筛选法分离培养Lewis大鼠骨髓间充质干细胞,流式细胞术检测其表面分子CD34、CD44的表达。经Lewis大鼠尾静脉注射经体外培养至第3代的骨髓间充质干细胞,7d后腹腔注射抗乙酰胆碱受体单克隆抗体(mAb35)建立实验性自身免疫性重症肌无力动物模型,按照Lennon评分标准进行临床症状评分、Western blotting法检测肌肉组织中乙酰胆碱受体蛋白表达、流式细胞术检测外周血CD4+CD25+T细胞比率、酶联免疫吸附试验检测血清转化生长因子-β、干扰素-γ和IL-4表达变化。结果与生理盐水对照组相比,注射骨髓间充质干细胞的实验性自身免疫性重症肌无力大鼠模型临床评分降低(t=8.062,P=0.000),乙酰胆碱受体α蛋白表达水平升高(t=8.092,P=0.000);同时血清转化生长因子-β表达水平升高(t=9.859,P=0.000),干扰素-γ(t=9.040,P=0.000)和IL-4(t=3.320,P=0.004)表达水平降低,两组之间差异均有统计学意义(P<0.05)。结论骨髓间充质干细胞能够显著减轻实验性自身免疫性重症肌无力大鼠模型临床症状,减少乙酰胆碱受体缺失。其作用机制可能与分泌免疫抑制性细胞因子转化生长因子-β上调CD4+CD25+调节性T细胞表达水平,以及抑制炎性促进因子干扰素-γ和IL-4的分泌有关。     

正清风痛宁对偏头痛大鼠脑干IL-1β、TNF-α表达的影响

目的观察正清风痛宁对炎性细胞因子白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)在偏头痛大鼠脑干表达的影响。方法将60只Wistar大鼠(雌雄各半)随机分为空白对照组(空白组)、偏头痛模型组(模型组)、舒马普坦组及正清风痛宁高、中、低剂量干预组(高、中、低剂量组)共6组。除空白组外,其余5组大鼠均建立三酰甘油偏头痛模型,用免疫组化SP法测定各组大鼠脑干IL-1β、TNF-α阳性细胞数。结果 6组大鼠间IL-1β、TNF-α阳性细胞数比较差异有统计学意义(分别F=7.063,P=0.001;F=8.257,P=0.000);组间两两比较,模型组脑干IL-1β(18.9±8.17)、TNF-α(14.30±6.41)阳性细胞数较空白组(5.90±2.69、5.00±1.63)增多(分别t=-4.780、P=0.000,t=-4.444,P=0.000),舒马普坦组(2.80±2.15,t=6.026,P=0.000;0.00±0.00,t=7.052,P=0.000)、中剂量组(7.70±4.76,t=3.745,P=0.000;6.20±1.99,t=3.815,P=0.000)、高剂量组(7.80±5.90,t=3.482,P=0.003;5.90±2.88,t=3.778,P=0.001)IL-1β、TNF-α阳性细胞数均较模型组减少;低剂量组脑干IL-1β(13.5±4.30,t=1.849,P=0.081)、TNF-α(11.30±6.11,t=1.071,P=0.298)阳性细胞数与模型组比较差异均无统计学意义;与舒马普坦组比较,低剂量组(t=-7.037,P=0.000;t=-5.847,P=0.000)、中剂量组(t=-2.966,P=0.011;t=-9.858,P=0.000)、高剂量组(t=-2.517,P=0.022;t=-6.467,P=0.000)脑干IL-1β、TNF-α阳性细胞数均增多;与低剂量组比较,中(t=-2.858,P=0.011;t=-2.510,P=0.022)、高剂量组(t=-2.468,P=0.024;t=-2.527,P=0.021)脑干IL-1β、TNF-α阳性细胞数减少;中、高剂量组脑干IL-1β、TNF-α阳性细胞数差异无统计学意义(t=0.042,P=0.967;t=-0.271,P=0.790)。结论正清风痛宁可能抑制偏头痛大鼠炎性细胞因子IL-1β、TNF-α的表达。     

脑源性神经营养因子诱导大鼠骨髓基质细胞成为神经干细胞及其分化作用的实验研究

目的探讨脑源性神经营养因子(BDNF)诱导大鼠骨髓基质细胞(BMSCs)成为神经干细胞及其分化作用。方法取成年大鼠BMSCs,分别以BDNF和BDNF+RA(维甲酸)作为诱导物诱导,于诱导3d、7d后行巢蛋白(Nestin)、神经元特异烯醇化酶(NSE)、胶质纤维酸性蛋白免疫细胞化学染色。结果诱导3天后BDNF和BDNF+RA诱导组均有大量Nestin染色阳性细胞,BDNF+RA组阳性率高于BDNF组(P<0.01)。NSE、GFAP免疫阳性细胞在诱导3d后也有少量表达。诱导7天后BDNF和BDNF+RA诱导组Nestin阳性细胞明显减少,与诱导3天后比较差异有显著性(P<0.01),而NSE、GFAP阳性细胞数增多,与诱导3天后相比差异有显著性(P<0.01),且BDNF+RA组阳性率高于BDNF组(P<0.01)。结论联合应用BDNF与RA可提高BMSCs神经转化,并促进其向神经元及星形胶质细胞细胞分化。     

骨髓间质干细胞联合脑源性神经营养因子用于大鼠脑出血的实验研究

目的观察骨髓间质干细胞(MSCs)联合脑源性神经营养因子(BDNF)治疗大鼠脑出血(ICH)的疗效。方法建立大鼠ICH模型,体外培养标记纯化的MSCs,经侧脑室植入脑部,同时局部注入BDNF。记录对照组、BDNF组、MSCs组和MSCs+BDNF组7d、14d、21d大鼠神经功能改善程度;免疫组化法检测MSCs脑内迁移及分化;电子显微镜观察神经凋亡细胞。结果 MSCs组大鼠运动功能有明显改善,MSCs+BDNF组对ICH损伤的修复作用最明显。MSCs+BDNF组各时间点MSCs阳性细胞数及NEUN、GFAP、CNP免疫阳性细胞数均高于MSCs组(P<0.01),且MSCs+BDNF组神经细胞凋亡程度最轻。结论 MSCs脑部移植可促进大鼠ICH损伤部位结构和功能修复,BDNF对其修复具有协同作用。     

Th1/Th2型细胞因子在实验性自身免疫性神经炎发病机制中的作用

目的 建立P2多肽诱导的实验性自身免疫性神经炎(EAN)大鼠模型,探讨Th1/Th2型细胞因子在EAN发病机制中的作用.方法 实验组用100 μg或200 μg P257-81多肽加完全弗氏佐剂(FCA)免疫Lewis大鼠,对照组单用FCA免疫,致敏后每日对大鼠进行临床评分,比较高峰期最高评分.致敏第14天测定淋巴结细胞培养液上清干扰素(IFN)-γ、IL-4及IL-10的含量,并进行坐骨神经病理学检查.结果 实验大鼠瘫痪高峰期最高评分P257-81 200 μg组(3.6±0.3)显著高于100 μg组(2.2±0.6,P＜0.01);P257-81 200 μg组大鼠病程显著长于100 μg组;IFN-γ含量,两组实验大鼠均显著高于对照组[分别为(530.6±91.7)、(806.3±132.4)和(35.0±5.9)pg/ml,均P＜0.01],而P257-81 200 μg组显著高于100 μg组(P＜0.01);IL-4和IL-10含量,P257-81 100 μg组均显著高于对照组(均P＜0.01),P257-81 200 μg组显著低于对照组(P＜0.05,P＜0.01);坐骨神经病理可见EAN急性期以炎性细胞浸润为主,P257-81 200 μg组慢性期无炎性细胞浸润,而表现为多发性局灶性脱髓鞘和神经纤维崩解未恢复.结论 EAN临床表现随致敏原P257-81多肽剂量增加而加重;在EAN急性期,IFN-γ水平与EAN临床表现大致平行;EAN疾病具有自限性可能与IL-4和IL-10水平增高有关,而疾病迁延可能与IL-4和IL-10水平降低有关.     

骨髓基质细胞及血管内皮祖细胞共移植对局灶性脑缺血大鼠系列生长因子表达的影响

目的 观察经静脉移植骨髓基质细胞(BMSCs)及血管内皮祖细胞(EPCs)后血管内皮生长因子(VEGF)、基质细胞衍生因子-1(SDF-1)、碱性成纤维生长因子(bFGF)、胰岛素样生长因子-1(IGF-1)、转化生长因子β(TGF-β)、血小板源性生长因子(PDGF)、脑源性生长因子(BDNF)、胶质源性生长因子(GDNF)和神经生长因子(NGF)这9种细胞因子的表达. 方法 80只健康成年Wistar 大鼠按照随机数字表法分为模型对照组、BMSCs移植组、EPCs移植组及联合移植组,每组20只.线栓法建立大鼠大脑中动脉闭塞模型.造模24h后,分别取浓度为3x106个/mL的BMSCs、EPCs悬液及两者混合液1mL经鼠尾静脉移植入BMSCs移植组、EPCs移植组及联合移植组;模型对照组鼠尾静脉注射1 mL生理盐水.移植后7d,实时荧光PCR、Western boltting检测各组大鼠脑内生长因子的表达. 结果 联合移植组中bFGF、VEGF、BDNF mRNA表达水平最高,与其他3组比较差异均有统计学意义(P＜0.05).BMSCs移植组中NGF、GDNF、TGF-β mRNA表达水平最高,与其他3组比较差异均有统计学意义(P＜0.05),联合移植组次之.EPCs组中PDGF-BB、IGF-1、SDF-1 mRNA表达水平最高,与其他3组比较差异均有统计学意义(P＜0.05),联合移植组次之. 结论 BMSCs及EPCs联合静脉移植可上调脑内生长因子表达水平,为提高细胞移植效率提供了新的尝试途径.     

T细胞疫苗接种实验性自身免疫性神经炎的实验研究

目的建立P257-81-特异性T细胞系,在实验性自身免疫性神经炎(EAN)大鼠进行T细胞疫苗接种(TCV)的实验研究。方法P257-81多肽、IL-2和抗CD3/CD28单抗包被磁珠诱导扩增P257-81-特异性T细胞及非抗原特异性T细胞,将灭活T细胞接种大鼠,检测指标包括:瘫痪高峰期最大评分比较,淋巴细胞增殖试验、CD4 T/淋巴结单个核细胞及CD4 CD25 T/CD4 T细胞百分比测定、培养液上清IFN-γ及IL-10水平测定以及坐骨神经病理学检查。结果P257-81-特异性T细胞显著扩增,2周扩增近1000倍;P257-81-特异性TCV预防组无大鼠发病;P257-81-特异性TCV治疗组大鼠病情减轻,其坐骨神经炎性细胞浸润程度显著轻于对照组(P<0.001);P257-81-特异性TCV预防组和治疗组CD4 CD25 T/CD4 T细胞百分比及培养液上清IL-10水平均显著高于其对照组,培养液上清IFN-γ水平均显著低于其对照组(均P<0.001)。结论抗原 IL-2 CD3/CD28单抗包被磁珠刺激是一种高效、可靠的扩增抗原特异性T细胞方法;P257-81-特异性TCV能预防EAN发生,并可治疗已发生的EAN,其机制可能为:使CD4 CD25 调节性T细胞/CD4 T细胞比例上调,诱导致病性CD4 Th1细胞向保护性CD4 Th2细胞转换。     

嗅鞘细胞移植后大鼠损伤脊髓神经生长因子的表达

目的 研究嗅鞘细胞移植对大鼠损伤脊髓内的神经生长因子(NGF)表达的影响,以从NGF角度探讨嗅鞘细胞移植修复大鼠脊髓损伤的机制.方法 48只SD大鼠用NYU -Ⅱ撞击机(10g-25 mm)损伤T10脊髓制作脊髓损伤(SCI)模型,随机分为嗅鞘细胞组、DMEM组各24只;另设立正常对照组6只.将GFP-嗅鞘细胞细胞悬液移植入嗅鞘细胞组大鼠损伤处,DMEM组用单纯的DMEM/F12液代替,正常对照组不做任何处理.移植术后1d、7d、14 d、21 d,用BBB评分法测定脊髓运动功能,RT - PCR方法比较各时间点NGF表达差异.移植术后第21天应用免疫组化比较嗅鞘细胞组、DMEM组、正常对照组大鼠脊髓损伤区NGF的表达差异.结果 移植后1d、7d、14 d、21 d,嗅鞘细胞移植组运动功能评分均高于同期DMEM组.NGF表达量在术后第1天最高,第7天达峰值,之后缓慢降低.移植后第21天,嗅鞘细胞移植组脊髓NGF表达量高于同期DMEM组和正常对照组.结论 嗅鞘细胞移植可上调损伤脊髓NGF的表达,从而促进了损伤脊髓的修复.     

神经干细胞在脑损伤模型中的迁移、成活和神经生长因子表达

目的 探讨神经干细胞在脑损伤模型中的迁移、成活和神经生长因子(NGF)表达.方法 SD大鼠30只随机分为3组:正常对照组(n=5)、损伤组(n =10)和移植组(n=15).正常对照组不做任何处理,损伤组和移植组均制备脑损伤模型,且移植组大鼠从尾静脉注入外源性神经干细胞.并观察神经干细胞在大鼠脑内的迁移和存活情况,同时通过免疫组织化学染色检测各组大鼠脑内NGF阳性细胞数量.结果 神经干细胞移植2周后,其向脑损伤区域发生迁移,并在损伤区域聚集和存活;且移植组NGF阳性细胞数目较正常对照组和损伤组显著增多(p＜0.05).结论 外源性神经干细胞经尾静脉注射移植后能自动向脑损伤区域迁移、聚集并存活,并可促进受损脑内的NGF表达.     

Tau-induced neurodegeneration: mechanisms and targets

The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau’s functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications: hyperphosphorylation, ubiquitination, glycation, glycosylation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifications can alter tau’s biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and propose a mechanism of neurodegeneration.     

The effect of risperidone on reward‐related brain activity is robust to drug‐induced vascular changes

Dopamine (DA) mediated brain activity is intimately linked to reward‐driven cerebral responses, while aberrant reward processing has been implicated in several psychiatric disorders. fMRI has been a valuable tool in understanding the mechanism by which DA modulators alter reward‐driven responses and how they may exert their therapeutic effect. However, the potential effects of a pharmacological compound on aspects of neurovascular coupling may cloud the interpretability of the BOLD contrast. Here, we assess the effects of risperidone on reward driven BOLD signals produced by reward anticipation and outcome, while attempting to control for potential drug effects on regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Healthy male volunteers (n = 21) each received a single oral dose of either 0.5 mg, 2 mg of risperidone or placebo in a double‐blind, placebo‐controlled, randomised, three‐period cross‐over study design. Participants underwent fMRI scanning while performing the widely used Monetary Incentive Delay (MID) task to assess drug impact on reward function. Measures of CBF (Arterial Spin Labelling) and breath‐hold challenge induced BOLD signal changes (as a proxy for CVR) were also acquired and included as covariates. Risperidone produced divergent, dose‐dependent effects on separate phases of reward processing, even after controlling for potential nonneuronal influences on the BOLD signal. These data suggest the D2 antagonist risperidone has a wide‐ranging influence on DA‐mediated reward function independent of nonneuronal factors. We also illustrate that assessment of potential vascular confounds on the BOLD signal may be advantageous when investigating CNS drug action and advocate for the inclusion of these additional measures into future study designs.     

星形胶质细胞对天冬氨酸特异性半胱氨酸蛋白酶介导β淀粉样蛋白早期突触毒性作用的影响

目的探讨星形胶质细胞(astrocyte,AS)对天冬氨酸特异性半胱氨酸蛋白酶(cysteinyl aspartate specific proteinase,caspase)介导β淀粉样蛋白(β-amyloid,Aβ)早期突触毒性作用的影响,以期为进一步研究与血管性痴呆(vascular dementia,Va D)的发病机制奠定基础。方法以原代培养大鼠海马纯神经元体系(NE-S)及混合培养体系(MIX-S,主要包含神经元及AS)为研究对象,各体系分为6组:对照组、caspase-8抑制剂组、caspase-9抑制剂组、Aβ处理组、caspase-8抑制剂预处理加Aβ组和caspase-9抑制剂预处理加Aβ组。免疫荧光检测各组近胞体10μm段树突中突触后密度蛋白(postsynaptic density-95,PSD95)表达量的变化。结果 1在NE-S与MIX-S中,与对照组相比,caspase-8抑制剂组、caspase-9抑制剂组PSD95的表达量均无明显差异,Aβ处理组PSD95的表达量均显著降低(P均0.001)。2在NE-S中,与Aβ处理组相比,caspase-9抑制剂预处理加Aβ组PSD95的表达量显著回升至对照组水平,caspase-8抑制剂预处理加Aβ组则无显著改变;在MIX-S中的结果则相反,即caspase-8抑制剂预处理加Aβ组PSD95的表达量显著回升至对照组水平,而caspase-9抑制剂预处理加Aβ组则无显著改变。3MIX-S与NE-S两种培养系统间相比较,对照组间及Aβ处理组间PSD95的表达量均无显著差异,而caspase-8抑制剂预处理加Aβ组间及caspase-9抑制剂预处理加Aβ组间PSD95的表达量差异有显著性。结论在Aβ早期突触毒性作用中,AS参与caspase-8介导的死亡受体通路激活过程,且参与抑制神经元的线粒体通路。     

Ultrastructure of non-myelinated neurons during energy deprivation

Summary This paper examines the neuropathology of oxygen-glucose deprivation uncomplicated by stagnant conditions. Rabbit vagus nerves were pulled into asmulti-compartment perfusion chamber, stimulated five times per second and deprived of energy by substituting nitrogen and deoxyglucose for oxygen and glucose in the Locke's perfusate. After incubation the compartments were perfused with gluteraldehyde solution, and the nerves were prepared for electron microscopy. Fixation in the compartments ensured precise cross and longitudinal sections which permitted quantitative comparisons. Although the action potentials ceased in 45 min, 1 h of energy deprivation did not significantly affect the ultrastructure. After 2 h of deprivation the axons were smaller and flattened and microtubules appeared packed together. In the smallest axons the microtubules were gone, the neurofilaments were compacted and the few mitochondria had a dense, homogenous appearance. By 4 h the shrinking was extreme, yet 8% were swollen much larger than any of the controls. Longitudinal views showed these balloned areas were greatly expanded regions of the smallest axons. Both tiny and huge regions were devoid of microtubules and the swollen axons contained expanded mitochondria.Calcium is indirectly implicated in the pathogenesis by the concurrence of mitochondrial alteration as the microtubules disappear coupled with the known role of mitochondria in calcium regulation and the reported effect of high calcium on microtubual dissociation. In is suggested that axons first shrink as osmotially active molecules are used or washed out. After a time without energy the mitochondria can no longer regulate the intracellular calcium, microtubules dissociate, and calcium-activated phospholipases create osmotically active molecules. Finally, high-amplitude, disruptive swelling occurs.Supported, in part, by a Grant-in-aid from the American Heart Association with funds contributed by the American Heart Association, Kansas Affiliate and by the University of Kansas Biomedical Sciences Support Grant RR0737     

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

Positron emission tomography (PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including genetically-engineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.     

Norharman-induced motoric impairment in mice: neurodegeneration and glial activation in substantia nigra

Summary. The β-carboline norharman is present in cooked food and tobacco smoke and show structural resemblance to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. C57BL/6 mice were injected subcutaneously with norharman (3 and 10 mg/kg) twice per day for five consecutive days. Eighteen hours after the last dose an increased expression of glial fibrillary acidic protein and fluoro-jade staining were demonstrated whereas the number of tyrosine hydroxylase positive cells were unchanged in the substantia nigra. Two weeks after the last treatment a decreased motor activity was observed whereas cognitive functions remained intact. In cultured PC12 cells norharman treatment induced mitochondrial dysfunction and increased the number of caspase-3 and TUNEL-positive cells. The results demonstrate that norharman induced apoptosis in cultured cells as well as early neurodegeneration, glial activation and sustained motor deficits in mice and suggest that exposure to norharman may contribute to idiopathic Parkinson’s disease.     

轻型缺血性卒中静脉溶栓后双重抗血小板疗效观察

目的 观察rt-PA静脉溶栓联合双重抗血小板治疗轻型缺血性卒中的有效性及安全性。 方法 以2013年12月-2016年12月在石家庄市第一医院连续住院治疗的轻型缺血性卒中患者为研究 对象,将其随机分为对照组、溶栓+单抗组和溶栓+双抗组。对照组不进行静脉溶栓,长期口服阿 司匹林（100 mg/d）抗血小板治疗;溶栓+单抗组在rt-PA静脉溶栓（0.9 mg/kg,最大剂量90 mg）基 础上长期单用阿司匹林（100 mg/d）抗血小板治疗;溶栓+双抗组在溶栓后单抗基础上加用氯吡格雷 （75 mg/d）双重抗血小板治疗,双抗治疗21 d后改为阿司匹林长期单抗治疗。随访3个月,有效性指标 为3个月时NIHSS 0～1分、Barthel指数（Barthel index,BI）95～100分和mRS 0～1分的比例,3个月时缺 血性卒中的复发率;安全性指标为治疗24 h出血转化和症状性出血转化的发生率。另外比较三组间 基线和3个月时血清hs-CRP和IL-6的水平差异。 结果 研究共纳入85例患者,对照组28例,溶栓+单抗组28例,溶栓+双抗组29例,全部患者均完 成3个月随访,无死亡患者。对照组、溶栓+单抗组和溶栓+双抗组3个月随访时NIHSS 0～1分比例分 别为46.43%、78.57%和93.10%,BI 95～100分比例分别为53.57%、82.14%和89.66%,mRS 0～1分 的比例分别为50.00%、82.14%和93.10%,三组上述有效性指标差异均有统计学意义,两两比较显 示,溶栓+双抗组高于溶栓+单抗组和对照组,溶栓+单抗组高于对照组,差异均有统计学意义;对 照组、溶栓+单抗组和溶栓+双抗组3个月时缺血性卒中复发率分别为32.14%、7.14%和3.45%,差异 有统计学意义。安全性指标方面,三组均无出血转化事件。对照组、溶栓+单抗组和溶栓+双抗组3 个月时的hs-CRP水平分别为11.92±3.58 mg/L、9.04±2.85 mg/L和6.04±2.65 mg/L,IL-6水平分别为 26.18±4.65 ng/L、16.11±6.93 ng/L和12.84±2.57 ng/L,三组上述炎症因子水平差异均有统计学意 义,其中溶栓+双抗组低于溶栓+单抗组和对照组,溶栓+单抗组低于对照组。 结论 对于急性轻型缺血性卒中患者,rt-PA静脉溶栓治疗后短期双重抗血小板治疗可显著改善患 者神经功能,降低炎症因子水平,降低复发率,且不增加出血风险。     

The ENIGMA‐Epilepsy working group: Mapping disease from large data sets

Epilepsy is a common and serious neurological disorder, with many different constituent conditions characterized by their electro clinical, imaging, and genetic features. MRI has been fundamental in advancing our understanding of brain processes in the epilepsies. Smaller‐scale studies have identified many interesting imaging phenomena, with implications both for understanding pathophysiology and improving clinical care. Through the infrastructure and concepts now well‐established by the ENIGMA Consortium, ENIGMA‐Epilepsy was established to strengthen epilepsy neuroscience by greatly increasing sample sizes, leveraging ideas and methods established in other ENIGMA projects, and generating a body of collaborating scientists and clinicians to drive forward robust research. Here we review published, current, and future projects, that include structural MRI, diffusion tensor imaging (DTI), and resting state functional MRI (rsfMRI), and that employ advanced methods including structural covariance, and event‐based modeling analysis. We explore age of onset‐ and duration‐related features, as well as phenomena‐specific work focusing on particular epilepsy syndromes or phenotypes, multimodal analyses focused on understanding the biology of disease progression, and deep learning approaches. We encourage groups who may be interested in participating to make contact to further grow and develop ENIGMA‐Epilepsy.     

缺血性卒中并发2型糖尿病患者颈动脉斑块内新生血管分布特点的超声造影研究

目的 应用超声造影观察缺血性卒中并发2型糖尿病患者颈动脉斑块内新生血管分布情况,明确其 斑块内新生血管分布特征。 方法 病例组选取因急性缺血性卒中住院的糖尿病患者40例（入组前未服用降糖药）,卒中同侧颈 动脉斑块形成;对照组为同期门诊就诊的颈动脉斑块形成患者,无卒中病史,性别及年龄匹配的非 糖尿病患者32例。两组患者行弓上计算机断层扫描血管造影（computed tomography angiography,CTA） 检查排除主动脉弓斑块及颅内动脉病变,排除卵圆孔未闭及心房颤动等。对所有患者均行常规超声 及超声造影检查。常规超声观察斑块厚度及内部回声,超声造影观察斑块增强情况,横切面多角度 观察,将超声造影结果分为近内膜处有增强（代表新生血管）及近内膜处无增强两种。 结果 两组患者颈动脉斑块厚度及回声情况差异无统计学意义。超声造影结果显示病例组颈动脉 斑块近内膜处增强者34例（85%）,对照组近内膜处增强12例（37.5%）,差异有统计学意义（χ 2=17.38, P＜0.01）。 结论 未服用降糖药的2型糖尿病并发急性缺血性卒中的患者颈动脉粥样硬化斑块内近内膜处新生 血管增生多于无糖尿病患者,提示血糖升高与颈动脉斑块内血管新生有关。     

Yohimbine increases the binding potential for [11C]flumazenil in the monkey brain

Summary. We evaluated the impact of yohimbine administration on benzodiazepine (BDZ) receptor binding in the central nervous system of non-human primates (rhesus monkeys). Estimates of the binding potential (B_max/K_d) of BDZ receptors were made following intravenous administration of yohimbine, an α₂-adrenoceptor antagonist. Positron emission tomography was used in conjunction with [¹¹C]flumazenil (Ro 15-1788), a tracer for central BDZ receptor binding activity. The effects of yohimbine were compared with a control condition in which saline was administered. Yohimbine significantly increased the binding potential in the hippocampus, as assessed using a Student's t-test with Bonferroni correction. The result that the administration of yohimbine readily induces an increase in the binding potential for BDZ receptors in the primate brain suggests that the presence of an anxiety state potentiates the effect of anxiolytics. Accepted August 10, 2001