海马注射Aβ25-35对大鼠CA1区tau蛋白和MAP2影响的研究

目的采用β-淀粉样蛋白（β-amyloid,Aβ）25—35注射法建立Alzheimer病（Alzheimer disease,AD）大鼠模型,观察该AD模型中tau蛋白和微管相关蛋白2（microtubule-associated protein-2,MAP2）表达情况。方法将健康雄性Wistar大鼠随机分成健康对照组、假手术组及AD模型组,以凝聚状态的Ap25—35经大鼠右侧海马注射制作AD模型,造模2周后应用HE染色和免疫组化方法,观察AD模型鼠脑中海马CA1区病理形态以及tau蛋白和MAP2的表达。结果AD模型组大鼠海马CA1区锥体细胞层紊乱、变稀、中断、数量减少,同时可见许多细胞体积缩小,胞核固缩且染色加深。AD模型鼠海马CA1区AD模型组tau蛋白阳性细胞（62．13±4．12）个／HP,较健康对照组[（26．78±3．46）个／HP3与假手术组[（26．36±3．13）个／HP]明显增高（均P〈0．01）;MAP2阳性细胞吸光度值AD模型组为5．13±4．12,较健康对照组（28．78±3．46）与假手术组（29．36±3．13）明显减少,差异有统计学意义（均P〈0．01）。结论在AB诱导的AD模型中tau蛋白表达增高,MAP2表达减低。     

应激对大鼠空间学习记忆的影响及与蛋白激酶活力的关系

目的探讨不同时段的应激对大鼠海马依赖性空间学习记忆的影响及与海马蛋白激酶A（PKA）、蛋白激酶C（PKC）和钙-钙调素依赖性蛋白激酶Ⅱ（CaMKⅡ）活力的关系。方法将60只雄性SD大鼠随机分为对照组、应激1次组、应激1周组、应激2周组和应激4周组，每组动物12只，其中应激模型为强迫大鼠游泳。应用Morris水迷宫（MWM）测试大鼠的空间学习记忆情况，采用同位素法检测蛋白激酶的活力。结果（1）MWM实验，应激1周组在第7和第8个实验中逃避潜伏期（EL）分别为（9．8±2．8）s和（9．8±4．6）s，少于其他4组（P〈0．01）；其他10个实验各组的EL相互比较，差异无统计学意义（P〉0．05）；记忆保留实验中，应激4周组的EL长于对照组（P〈0．05）；应激1周组大鼠60s内穿越原平台位置的次数[（3．24-1．2）次]多于对照组[（1．8±0．5）次；P〈0．05]。（2）应激1周组大鼠PKA和PKC活力[分别为（6．42±0．27）×10^-2和（4．71±0．37）×10^-2]高于对照组[分别为（5．53±0．49）×10^-2和（1．48±0．27）×10^-2；P〈0．01]；应激2周组和应激4周组PKA[分别为（4．88±0．23）×10^-2和（3．92±0．22）×10^-2]和PKC[分别为（0．57±0．03）×10^-2和（0．69±0．02）×10^-2]活力则低于对照组（P〈0．01）。各应激组海马CaMKⅡ的活力均明显低于对照组（P〈0．01）。结论慢性应激损害大鼠海马依赖性空间长时记忆，抑制大鼠海马PKA、PKC和CaMKⅡ的活力；短时间的重复应激选择性提高大鼠海马依赖性空间短时记忆，提高PKA和PKC活力。应激导致记忆改变可能与蛋白激酶活力变化有关。     

ω-3多不饱和脂肪酸对慢性轻度应激抑郁症大鼠糖水摄入量及脑单胺类递质的影响

目的探讨鱼油中的ω-3多不饱和脂肪酸（ω-3PUFA）对慢性轻度应激（CMS）抑郁症大鼠模型糖水摄入量及脑单胺类递质的影响，并探讨其可能的神经生化机制。方法雄性Sprague—Dawley大鼠41只，随机分为CMS组（32只）和正常组（9只），CMS组共CMS刺激8周，自实验第4周末起，随机分为ω-3PUFA组（8只）、阳性对照组（氯米帕明组，8只）和2个阴性对照组[橄榄油组（8只）和生理盐水组（8只）]。实验每周进行1次糖水消耗量的测定，实验第8周末采增高效液相色谱技术测定海马及前额叶皮质的5-羟色胺（5-HT）、去甲肾上腺素（NE）、多巴胺（DA）及其代谢产物的水平。结果（1）实验第8周末，ω-3PUFA组糖水摄入量[（10．25±1．55）g]均高于橄榄油组[（5．98±1．83）g]及生理盐水组[（4．65±1．17）g]，P=0．010和P=0．008；与氯米帕明组[（13．27±1．27）g]的差异无统计学意义（P〉0．05）。（2）ω-3PUFA组海马5-HT[（0．11±0．03）μg／g]、5-羟吲哚乙酸（5-HIAA）[（0．14±0．04）μg/g]及NE水平[（0．47±0．14）μg／g]均分别明显低于橄榄油组[（0．24±0．04）μg／g]、[（0．25±0．02）μg／g]、[（0．88±0．09）μg／g]及生理盐水组[（0．30±0．10）μg／g]、[（0．35±0．02）μg／g]、[（1．02±0．05）μg／g]，DA水平[（0．09±0．06）斗g／g]高于橄榄油组[（0．02±0．00）μg／g]，差异均有统计学意义（P均〈0．05）。（3）与橄榄油组相比，ω-3PUFA组前额叶5-HT水平[（0．08±0．01）μg／g]降低、DA水平[（0．04±0．00）μg／g]升高，差异均有统计学意义（P均〈0．05）。前额叶和海马所有单胺类递质的水平与氯米帕明组的差异均无统计学意义（P均〉0．05）。结论ω-3PUFA能够明显缓解慢性轻度应激大鼠糖水摄入量的降低，多种单胺类递质可能参与了该现象的作用机制。     

慢性束缚应激对大鼠行为及前额叶皮质细胞外信号调节激酶磷酸化的影响

目的 探讨慢性束缚应激模型大鼠的行为及前额叶皮质中磷酸化细胞外信号调节激酶（ERK1／2）表达的变化。方法 将雄性SD大鼠随机分为正常对照组和束缚应激组，每组8只。将束缚应激组大鼠放入特制的束缚器中限制其活动，6k／d，连续21d。比较应激前后大鼠旷场行为和Morris水迷宫行为学的改变，用蛋白免疫印迹技术和免疫组织化学方法观察应激后大鼠前额叶皮质P—ERK1／2表达的变化，并与正常对照组比较。结果 （1）行为学改变：应激后，束缚应激组大鼠的水平活动度[（4265±864）mm]少于正常对照组[（8562±502）mm]，中央停留时间[（39．1±4．3）s]长于正常对照组[（24．6±1．6）s]，均P〈0．01；束缚应激组大鼠在Morris水迷宫实验的目标象限活动时间[（57．2±1．7）s]和穿越站台次数[（2．0±0．8）次]均少于正常对照组[分别为（70．7±3．6）s和（6．2±1．0）次；均P〈0．01]。（2）p-ERK1／2蛋白水平：应激后束缚应激组吸光度（A）值[（0．767±0．006）]低于正常对照组[（0．813±0．015）；P〈0．05]。（3）p-ERK1／2阳性细胞数：应激后束缚应激组[（76±5）个]少于正常对照组[（110±14）个；P〈0．05]，且树突染色浅淡。结论 慢性心理应激明显影响动物的活动度和记忆能力；前额叶皮质中p-ERK1／2表达的减少，提示ERK信号转导通路可能参与了应激发生的机制。     

氟西汀对慢性应激大鼠海马S100B和糖基化代谢终产物受体表达的影响

目的 探讨氟西汀对慢性应激大鼠海马S100B和晚期糖基化代谢终产物受体（RAGE）含量的影响。方法 将雄性sD大鼠4J0只随机分为正常对照组（以下简称对照组）、抑郁组、氟西汀（10mg·kg^-1，腹腔注射）＋抑郁组（F＋抑郁组）、氟西汀（10mg·kg^-1，腹腔注射）＋对照组（F＋对照组），每组各10只。采用21d不可预见性中等强度应激造成大鼠抑郁模型，于应激前及应激第22天观察大鼠行为（体质量、24h饮用1％蔗糖溶液量、旷场实验）；以Western blotting和激光共聚焦显微镜测定药物对各组大鼠海马S100B及RAGE表达水平的影响。结果 （1）在应激第22天，抑郁组大鼠体质量、蔗糖溶液消耗量、直立次数均低于对照组（P〈0．05），水平运动格子数低于对照组（P〈0．01），粪便颗粒数多于对照组（P〈0．05）；F＋抑郁组体质量、蔗糖溶液消耗量、水平运动格子数、直立次数均高于抑郁组（P〈0．05）。（2）抑郁组大鼠海马S100B[荧光强度18±5，吸光度（A）值3．24土0．45]、RAGE（荧光强度16±5，A值2．89±0．24）水平较对照组S100B（荧光强度25±7，A值5．28±0．48）、RAGE（荧光强度24±6，A值5．68±0．29）明显降低（P〈0．05），F＋对照组S100B（荧光强度31±5，A值7．34±0．29）、RAGE（荧光强度30±4，A值7．43±0．32）表达水平高于对照组（P〈0．05），而F＋抑郁组S100B（荧光强度23±3，A值5．00±0．34）、RAGE（荧光强度22±4，A值4．93±0．54）表达水平明显高于抑郁组（P〈0．05）。结论 慢性应激下调大鼠S100B，RAGE蛋白表达水平，而氟西汀上调S100B，RAGE的表达水平。     

锂对慢性铝暴露大鼠学习记忆功能的影响及其机制

目的 探讨锂对慢性铝暴露大鼠学习记忆功能以及脑内淀粉样B蛋白前体（APP）代谢的影响。方法 将24只慢性铝暴露大鼠随机分为锂治疗组和非治疗组，每组12只；另取12只非铝暴露大鼠为正常组。锂治疗组给予氯化锂溶液（200mg·kg^-1·d^-1）灌胃，非治疗组以等量氯化钠溶液灌胃，正常组大鼠不进行干预。6周后Morris水迷宫测试，比较三组大鼠的学习记忆功能；分别采用免疫组织化学法和免疫印迹法检测各组大鼠脑组织内淀粉样B蛋白（AB）和APP含量。结果 （1）锂治疗组大鼠定向航行实验潜伏期[（15．4±8．7）s]短于非治疗组[（26．8±11．2）s；F=-3．8，P〈0．05]，空间搜索中随机式所占比例（11．1％）低于非治疗组（20．7％；P〈0．05），站台停留时间[（47±7）s]和穿台次数[（12．6±2．2）次]多于非治疗组[（35±7）s和（7．9±2．6）次；P〈0．05]；（2）正常组大鼠脑内APP的含量（1．0±0．3）低于其他两组[锂治疗组为（1．8±0．4），非治疗组为（1．8±0．5）；P〈0．01]。非治疗组脑内海马、皮层AB反应阳性数目多于其他两组（P〈0．01）。结论 锂可以改善慢性铝暴露大鼠学习记忆功能，可能是通过抑制B分泌酶裂解途径而影响APP的代谢，减少AB的产生。     

广泛性焦虑患者视觉任务的功能磁共振成像研究

目的　观察广泛性焦虑患者处理情绪图片的脑功能定位，探讨其可能的精神病理机制。方法　对9名广泛性焦虑患者（研究组）和9名健康对照者（对照组）评定汉密尔顿焦虑量表（HAMA）和焦虑状态特质问卷（STAI），并在完成国际情绪图片系统中的正性、中性、负性三种图片主动注视任务中，按照区块设计，应用Marconi　1．5T磁共振仪横断位扫描脑功能磁共振成像（fMRI）。结果　（1）研究组HAMA[（27．7±5．8）分]、STAI特质评分[（43．0±14．4）分]和状态评分[（40．6±5．8）分]均高于对照组[分别为（1．8±1．3）分、（30．0±8．3）分和（32．4±5．2）分；P〈0．05—0．01]；两组对三组图片的愉悦度评价差异均无统计学意义（P〉0．05）。（2）fMRI：两组比较，研究组右中央前回（t=5．009）、右海马（t=5．345）、右舌回（t：4．584）激活增强，右额中回（t=-5．095）、左旁中央小叶（t=-5．358）、右颞中回（t=-5．074）、右梭状回（t＝-8．833）、左枕中回（t=-8．100）、右枕中回（t=-5．570）、右小脑扁桃体（t=-4．654）激活减弱，差异有统计学意义（P〈0．001）。结论　广泛性焦虑患者脑功能异常表现以右侧为主，主要是右侧额中回、右侧海马、右侧小脑和枕叶等区域异常。     

利培酮与舒必利对精神分裂症男性老年患者血清催乳素水平影响的对照研究

目的 探讨利培酮和舒必利对精神分裂症男性老年患者血清催乳素（PRL）水平的影响。方法 将51例精神分裂症男性老年患者随机分为利培酮组[（3．7±0、9）mg／d，24例]和舒必利组[（800±156）mg／d，27例]，采用酶联免疫方法测定两组治疗前后的PRL水平，并与25名正常男性老年人（对照组）进行对照。结果 （1）治疗前，患者组PRL水平[（26±11）彬L]与对照组[（24±14）μg／L]的差异无统计学意义，利培酮组[（26±11）μg/L]与舒必利组[（28±12）μg/L]的差异亦无统计学意义（均P〉0．05）。（2）治疗后，患者组PRL水平[（149±59）μg/L]高于治疗前（t=14．53，P〈0．01）；利培酮组[（118±47）μg/L]和舒必利组[（196±73）μg/L]亦均高于治疗前，其中舒必利组高于利培酮组（均P〈0．01）。结论 利培酮和舒必利均能升高精神分裂症男性老年患者的PRL水平，其中以舒必利更为显著。     

儿童精神分裂症患者微小躯体异常与脑室扩大关系的研究

目的探讨儿童精神分裂症患者微小躯体异常（MPAs）与脑室扩大的关系。方法对168例儿童精神分裂症患者（患者组）进行躯体异常量表（WS）评定，并将患者分为MPAs明显组（WS总分≥4分，85例）和MPAs不明显组（WS总分≤3分，83例）。用阳性和阴性症状量表（PANSS）评定患者组的精神症状；用CT测量患者的脑室（脑室值用哈氏值、三脑室宽度、脑室指数、侧脑室体部指数、侧脑室宽度指数、前角指数表示），并与40名健康儿童（对照组）进行对照。结果（1）患者组哈氏值[（5．37±0．53）cm]和三脑室宽度[（3．83±1．21cm）]均大于对照组[分别为（4．94±0．34）cm和（3．16±0．41）cm]，腩室指数（1．55±0．18）和前角指数（3．52±0．31）小于对照组（分别为1．65±0．22和3．77±0．34），均P〈0．01。（2）MPAs明显组哈氏值[（5．50±0．54）cm]和三脑室宽度[（4．10±1．32）cm]大于MPAs不明显组[分别为（5．24±0．49）cm和（3．55±1．01）cm]和对照组，前角指数（3．47±0．30）小于MPAs不明显组（3．57±0．31）和对照组，脑室指数（1．55±0．18）小于对照组。（3）MPAs不明显组哈氏值大于对照组，脑室指数和前角指数小于对照组，均P〈0．01和P〈0．05。（4）患者组WS总分与哈氏值（r=0．263）及三脑室宽度（r=0．287）存在正相关，与前角指数存在负相关（r=-0．178）；患者组的WS总分与阴性症状分呈正相关（r=0．247）；患者组的阴性症状分与哈氏值（r=0．375）和三脑室宽度（r=0．161）呈正相关，与脑室指数（r=-0．159）和前角指数（r=-0．191）呈负相关（均P〈0．01和P〈0．05）。结论儿童精神分裂症患者存在显著的MPAs和脑室扩大，MPAs与脑室扩大之间有明显的相关。     

纳洛酮对铝致学习记忆减退大鼠海马锥体细胞凋亡的影响

目的观察纳洛酮对铝致学习记忆减退大鼠海马锥体细胞凋亡的影响。方法采用慢性氯化铝灌胃方法,制备学习记忆减退大鼠模型后随机分为模型组和纳洛酮治疗组,另设正常对照组。纳洛酮治疗组大鼠连续7 d腹腔注射纳洛酮。采用脱氧核苷酸末端转移酶介导的脱氧尿苷酸-生物素切口末端标记法,原位检测凋亡细胞,流式细胞仪检测凋亡率。结果纳洛酮组大鼠海马锥体细胞的凋亡率为（6.4±1.6）%,模型组（9.6±1.9）%,差异有统计学意义（P〈0.05）;纳洛酮组大鼠凋亡细胞数为（7.5±1.9）,模型组（12.8±2.2）,差异有统计学意义（P〈0.05）。结论纳洛酮能减少铝致学习记忆减退大鼠海马锥体细胞的凋亡。     

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.     

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.     

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。     

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